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New Hypertension Cure
Hypertension Exercise Program
The exercises in Three Easy Exercises to Drop Blood Pressure Below 120/80 take about 30 minutes a day, and you can do them while you're doing routine household chores. Christian Goodman is the researcher behind the Blue Heron Health High Blood Pressure Exercise Program. If this pressure is too high, it puts a strain on your arteries and your heart making you more likely suffer a heart attack, a stroke or kidney disease. All of your risk will be stopped instantly in less than 30 minutes a day to practice exercises. These exercises used in Natural Blood Pressure are focused on mind and body ones in the system called Focused Break. You will start experiencing the calming effects of the exercises within minutes. Best of all, you won't need to rely on medication or implement any major dietary changes. They're safe, easy and effective. More here...
Hypertension Exercise Program Summary
Contents: Ebook
Author: Christian Goodman
Official Website: blueheronhealthnews.com
Price: $49.00
My Hypertension Exercise Program Review
Recently several visitors of websites have asked me about this ebook, which is being promoted quite widely across the Internet. So I ordered a copy myself to figure out what all the fuss was about.
My opinion on this e-book is, if you do not have this e-book in your collection, your collection is incomplete. I have no regrets for purchasing this.
Antihypertensive Actions of Vitamin B6
Vitamin B6 depletion leads to the development of hypertension in experimental animals, which is normalized within 24 hours by repletion with the vitamin. 4. Increased end-organ responsiveness to glucocorticoids, mineralocorti-coids, and aldosterone (Section 9.3.3). Oversecretionof (andpresumably also enhanced sensitivity to) any of these hormones can result in hypertension. Vitamin B6 supplementation would be expected to reduce endorgan sensitivity to these hormones, and thus might have a hypotensive action. A number of studies suggest that supplements of vitamin B6 may have a hypotensive action. Supplements of 300 mg of vitamin B6 per kg of body weight per day attenuated the hypertensive response of rats treated with deoxycor-ticosterone acetate (Fregly and Cade, 1995). At a more realistic level of supplementation (five times the usual amount provided in the diet), vitamin B6 prevented the development of hypertension in the Zucker (fa fa) obese rat. Withdrawal of the vitamin...
Asthenia And Familial Hypertension And Diabetes
Fig. 7.9 Clusters of points with low ESR in 26 patients with familial hypertension but who themselves have normal blood pressure values on the left cluster of tender points with PPT of the same subjects on the right. The colored sectors correspond to a significantly higher concentration of points, respectively, for ESRT vs. PPT on the left side or for PPT vs. ESRT on the right side of the figure. Colored areas lateral surface blank areas medial surface. Fig. 7.9 Clusters of points with low ESR in 26 patients with familial hypertension but who themselves have normal blood pressure values on the left cluster of tender points with PPT of the same subjects on the right. The colored sectors correspond to a significantly higher concentration of points, respectively, for ESRT vs. PPT on the left side or for PPT vs. ESRT on the right side of the figure. Colored areas lateral surface blank areas medial surface. It is interesting, in my opinion, to see how these patterns of distribution of...
Isolated systolic hypertension
There are three main reasons why isolated systolic hypertension has become increasingly important over the past few years We are seeing more and more elderly patients, and isolated systolic hypertension is the most common form of high BP in the geriatric population. The treatment goals of systolic BP have become increasingly lower over the past few years, thereby creating numerous hypertensive patients who, according to previous criteria, would not have fulfilled this definition. Even in very elderly patients, a systolic BP goal of less than 140 mmHg can be a realistic goal with modern antihypertensive therapy, although sometimes The most common pitfall encountered in the treatment of isolated systolic hypertension is the failure to recognize that bradycardia can be its major perpetrator. Any decrease in heart rate is prone to an increase in stroke volume a higher stroke volume ejected into a stiff aorta will elevate systolic and lower diastolic pressure. Thus, bradycardia often...
Hypertension High Blood Pressure
When pressure exerted by blood on the walls of the arteries is greater than normal, blood pressure rises. Usually, blood pressure falls when at rest. It rises in response to strenuous physical activity, stress, or a perceived danger in which the sympathetic nervous system dominates, arteries constrict, and more blood is sent to the brain increasing blood pressure. This heightened state of the sympathetic system does not seem to retreat in individuals with hypertension and damage to the heart, kidney, arteries, and other organs becomes inevitable. Blood pressure is considered high at a reading of 140 90. There are no symptoms of the illness and it is recommended individuals over 40 be checked. Hypertension can be controlled by permanent diet and lifestyle changes this includes reducing stress, maintaining proper weight (not more than 5 lb overweight), and eating foods containing compounds that reduce blood pressure such as celery, garlic, and fresh fruits and vegetables. Having a home...
Early morning hypertension
Ever since the pioneering studies of Sir George Pickering, we have known that BP follows a distinct diurnal pattern, decreasing throughout the evening to a nadir at midnight, followed by an early morning rise shortly before awakening. This pattern is qualitatively similar in both normotensive and hypertensive patients. Hypertensive complications, such as stroke, acute MI, and sudden death follow a very similar pattern the time period between 6 00 a.m. and 10 00 a.m. seems to confer the highest risk for these events. In a meta-analysis of 31 studies, Elliott showed a 49 higher stroke risk in the period from 6 00 a.m. to noon than in the remaining hours ofthe day 81 . Similarly, Kario etal. 82 showed a higher prevalence of silent cerebral ischemia and stroke in patients who have a morning surge of BP, as opposed to patients who did not exhibit such a surge. Although the exact relationship between BP and the occurrence of these events remains to be elucidated, good BP control during the...
Antihypertensive efficacy
Concomitant medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), or a high salt intake can mitigate the antihypertensive efficacy of certain drug classes, such as ACE inhibitors or ARBs. Beta-blockers have little, if any, effect in isolated systolic hypertension in elderly patients. A high salt intake can counteract the effects of diuretics and blockers of the RAS. In contrast, few, if any, drugs or dietary interventions affect the efficacy of calcium antagonists. Calcium antagonists, of which amlodipine is the prototype, lower BP regardless of age, sex, race, diet, concomitant diseases, or medications. Numerous prospective randomized trials have documented that calcium anatagonists reduce the rate of stroke and heart attack. From an
Hypertension as a gateway to cardiovascular risk modification
Measurement of BP is a simple, straightforward procedure that allows us to identify the risk of cardiovascular disease. However, treatment of raised BP is clearly inefficient to reduce the overall associated cardiovascular disease risk. Antihypertensive therapy should, therefore, serve as a gateway to overall cardiovascular risk management and give rise to normal risk estimation. This can be done by using the Framingham risk score 1 or the systems put forward by the European Society of Cardiology 24 and others. We have learned recently that the use of more elaborate risk assessment by a series of biomarkers does not really add much to additional methods of assessing the cardiovascular disease risk. However, one ofthe most important criticisms of cardiovascular risk estimation is that it is based on limited time projections, most often on 10-year absolute risk estimation. This approach strongly favors treatment of the elderly population because age is a more powerful determinant of the...
Hypertension And Cholesterol Lowering
CoQ10 has been studied both as stand-alone and adjunctive treatment in hypertension. According to a review of 8 studies, supplemental CoQ10 results in a mean decrease in systolic blood pressure of 16 mmHg and in diastolic blood pressure of 10 mmHg (Rosenfeldt et al 2003). The effect on blood pressure has been reported within 10 weeks of treatment at doses usually starting at 100 mg daily. One small 10-week open study of 26 subjects with essential hypertension study found that an oral dose of 50 mg taken twice daily also reduced total serum cholesterol levels with a
Lifestyle Treatment of Hypertension
Most of the risk factors for primary hypertension are preventable, and lifestyle modification may prevent as well as treat the condition. Secondary hypertension can be managed by treating the underlying cause. Individuals in the high normal and stage 1 hypertension categories should attempt to lower blood pressure through diet and lifestyle changes before going on a regimen of medications. Recommendations include Onusko, E. (2003). Diagnosing Secondary Hypertension. American Family Physician 67 67-74. Also available from
Pharmacological Treatment of Hypertension
Hypertension is commonly treated with medication, and a combination of two or more drugs is common. Patients are usually given a diuretic to help them excrete excess fluids. However, most diuretics also cause excretion of potassium in the urine, and individuals on diuretics should monitor their potassium intakes. Drugs used to control hyertension include beta-blockers (e.g., atenolol Tenorim ) which act to slow heart rate and cause some vasodilation (widening of the lumen, or interior, of blood vessels). Drugs that contain calcium channel blockers (e.g., amlopidine Norvasc ) or angiotensin-converting enzyme (ACE) inhibitors also cause vasodilation.
Diet and Hypertension
Sodium intake has been a primary target for hypertension control, though it is ranked fourth as the lifestyle factor associated with hypertension. About 50 percent of individuals appear to be sodium sensitive. This means that excessive sodium intake tends to increase blood pressure in these groups of people, and they do not appear to excrete excessive amount of salt via the kidneys. Sodium-sensitive individuals include the elderly, obese individuals, and African Americans. The Dietary Guidelines for Americans recommend that adults consume no more than 2,400 milligrams of sodium daily. There are a number of ways to limit sodium in the diet, including Potassium supplements (2-4 grams daily) have been shown to moderately decrease blood pressure. Fruits and vegetables are excellent sources of potassium. The Dietary Guidelines for Americans recommend that adults consume at least 3,500 milligrams of potassium daily. A diet high in fruits and vegetables has been linked to a decreased risk of...
Causes of Hypertension
Many prescription and over-the-counter drugs can cause or exacerbate hypertension. For example, corticosteroids and immunosuppressive drugs increase blood pressure in most solid-organ transplant recipients. Medication taken for pain and inflammation such as nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may raise blood pressure since their antiprostaglandin properties affect the kidneys. There does not appear to be a direct relationship between caffeine and chronic hypertension, even though caffeine intake can cause an acute (rapid but brief) increase in blood pressure. This may be due to the fact that tolerance to caffeine develops rapidly. Chronic overuse of alcohol is a potentially reversible cause of hypertension. Five percent of hypertension is due to alcohol consumption and 30 to 60 percent of alcoholics have hypertension. Alcohol-induced hypertension is more likely to occur in women than men.
Resistant hypertension
Resistant hypertension is said to be present if, despite triple therapy including a thiazide diuretic, BP remains distinctly above target range. Figure 31 lists some of the more common underlying causes of resistant hypertension. Of particular concern are NSAIDs, as well as the cyclooxygenase 2 (COX2) inhibitors. These drugs elevate BP by a variety of mechanisms, ranging from direct binding with mineralocorticoid receptors to interference with prostaglandin synthetase. Very often, the antihypertensive efficacy of ACE inhibitors and ARBs is completely abolished when NSAIDs, or COX2 inhibitors, are added to the regimen. In contrast, these drugs have little, if any, effect on the antihypertensive efficacy of calcium antagonists. Perhaps the most common error is to diagnose resistant hypertension when triple antihypertensive therapy is given without a diuretic. In volume-expanded patients, in those who abuse salt, and in black patients, the antihypertensive efficacy of ACE inhibitors and...
Whitecoat hypertension and masked hypertension
BP is a very labile hemodynamic parameter it varies from heartbeat to heartbeat, from morning to evening, from winter to summer, from sleeping to awake, and from sitting to standing. The same holds true for any other cardiovascular hemodynamic parameter, such as heart rate, cardiac output, ejection fraction, or pulmonary wedge pressure. However, the information that is based on invasively obtained measurements is often considered more reliable than information based on simple BP recording. Numerous studies have documented that BP carefully measured by cuff, under standardized conditions in physicians' offices, is a powerful and reliable predictor of morbidity and mortality. More recent studies have documented that 24-hour ambulatory BP monitoring is an even closer surrogate end point for heart attack and stroke than is office-measured BP. As the correlation between 24-hour ambulatory BP measurement and office BP measurement is moderate at best, there will be, not unexpectedly, a...
Preexisting Chronic Hypertension
Mild and uncomplicated chronic hypertension during pregnancy has a better prognosis than pre-eclampsia. However, there is an increased risk of superimposed pre-eclampsia and possible complications if preexisting renal disease or systemic illness is present. The primary aim of therapy, if necessary, is to prevent cerebrovascular complications and to avoid progression to superimposed pre-eclampsia with its worse prognosis. Nonpharmacological management of this condition during pregnancy remains controversial. In a published review of management of mild to chronic hypertension during pregnancy, no trials were found that compared nonpharmacological interventions with either pharmacological agents or no intervention in pregnant women. This comprehensive search identified 50 randomized controlled trials, but they involved either normotensive women or women with a history of pre-eclampsia. For the management of established chronic hypertension during pregnancy, no relevant evidence could be...
Hypertension in Pregnancy
Pregnancy-induced hypertension is a syndrome characterized by hypertension, proteinuria, and edema. This condition usually develops in the third trimester and occurs in approximately 7 or 8 of pregnant women. It occurs more often in women who are young, pregnant for the first time, or are of low socioeconomic status. The exact cause of this condition is unknown, but most researchers agree that it is associated with a decreased uterine blood flow leading to reduced fetal nourishment. Previous treatments for this condition included sodium restriction and diuretics however, neither of these has been successful in altering blood pressure, weight gain, or proteinuria in this condition.
Antihypertensive Effects
High blood pressure is associated with decreased life expectancy and increased risk of stroke, coronary heart disease, and other end-organ diseases such as renal failure. Ginseng contains active compounds that normalize blood pressure. The effect of a certain drug on blood pressure can be analyzed by investigating the effect of the drug on the smooth muscle of blood vessels. It is well established that blood vessel smooth muscle tone is regulated by the available intracellular Ca2+ concentration, which in turn is profoundly influenced by interaction of the cellular membrane and sarcoplasmic reticu-lum in the smooth muscle. It was found that both protopanxatriol and protopanaxadiol saponins inhibit Ca2+ binding to the cellular membrane protopanaxatriol is approximately 180 more potent than protopanaxadiol ginsenosides (76). It was reported that ginseng induced no significant change in blood pressure in subjects with normal blood pressure, but had a normalizing effect on subjects with...
Dietary Factors That Lower Blood Pressure
Additional trials have documented that modest weight loss can prevent hypertension by approximately 20 among overweight, prehypertensive individuals and can facilitate medication step-down and drug withdrawal. Lifestyle intervention trials have uniformly achieved short-term weight loss, primary through a reduction in total caloric intake. In some instances, substantial weight loss has also been sustained over 3 or more years. In aggregate, available evidence strongly supports weight reduction, ideally attainment of a body mass index less than 25 kg m2, as an effective approach to prevent and treat hypertension. Weight reduction can also prevent diabetes and control lipids. Hence, the One of the most important dose-response trials is the DASH-Sodium trial, which tested the effects of three different salt intakes separately in two distinct diets the DASH (Dietary Approaches to Stop Hypertension) diet and a control diet more typical of what Americans eat. As displayed in Figure 3, the...
Blood pressure lowering in prehypertensive patients
The JNC created a new BP class in 2003 called prehypertension 2 . The issue surrounding this entity has stirred tempers to an extent that seems more suitable to medieval theologians than to modern scientists. The extensively quoted meta-analysis of Lewington 33 suggested a continuous relationship between the risk of cardiovascular disease (stroke, coronary heart disease, and vascular disease) and usual BP values down to at least 115 75 mmHg. In the Framingham cohort 1 , an increase in cardiovascular events was reported in individuals with a higher baseline BP within the normotensive range (ie, below 140 90 mmHg). In this cohort of normotensive subjects, BP levels paralleled cardiovascular disease risk in the same way as they did in hypertension. It follows that normotensive individuals with a host of additional risk factors could be at higher overall cardiovascular risk than patients without risk factors with mild hypertension. It follows further that the absolute benefits of...
A1 Lifestyle Trials in Hypertensive Patients
Evidence Statement Weight loss produced by lifestyle modifications reduces blood pressure in overweight hypertensive patients. Evidence Category A. Rationale A 1987 meta-analysis 381 covering five of the acceptable studies 351, 352, 356-358 in hypertensive patients concluded that weight loss accomplished by dietary interventions significantly lowered blood pressure. In hypertensive patients, Since publication of this meta-analysis in 1987, almost all relevant studies have reported that weight loss reduces blood pressure or the need for medication in hypertensive patients 346- 348, 350, The Trial of Antihypertensive Interventions and Management (TAIM), conducted in hypertensive individuals not taking medication for 6 months, reported that, compared with controls, a mean net weight reduction of 4.7 kg (10.4 lb) reduced systolic and diastolic blood pressure by 2.8 mm Hg and 2.5 mm Hg, respectively 355 the effects on blood pressure were equivalent to drug therapy among those participants...
Antihypertensive therapy in physically active patients
Lifestyle modifications often have to be adapted to fit a specific antihypertensive therapy and vice versa. Regular aerobic exercise has a mild antihypertensive effect, probably because oflow-grade, chronic fluid volume and salt depletion. Thus, aerobic exercise should be encouraged in all patients with hypertension conversely, drugs that decrease aerobic exercise performance, such as beta-blockers and, to a lesser extent, diuretics, should be avoided in the physically active patient. Fluid and salt depletion associated with diuretic therapy may make the patient more prone to dehydration during prolonged aerobic exercise. Isometric exercise (weightlifting) is relatively contraindicated in patients with hypertension because of the excessive spikes in systolic pressure that have been documented during strenuous weightlifting. Profound hypotension can be observed in patients on ACE inhibitors or ARBs, together with dehydration, such as that which occurs when running or when undertaking...
Types of Hypertension
Hypertension is classified as either primary (or essential) hypertension or secondary hypertension. Primary hypertension has no specific origin but is strongly associated with lifestyle. It is responsible for 90 to 95 percent of diagnosed hypertension and is treated with stress management, changes in diet, increased physical activity, and medication (if needed). Secondary hypertension is responsible for 5 to 10 percent of diagnosed hypertension. It is caused by a preexisting medical condition such as congestive heart failure, kidney failure, liver failure, or damage to the endocrine (hormone) system. Pregnancy-induced hypertension (PIH) may appear in otherwise healthy women after the twentieth week of pregnancy. It is more likely to occur in women who are overweight or obese. PIH may be mild or severe, and it is accompanied by water retention and protein in the urine. About 5 percent of PIH cases progress to preeclampsia. Preeclampsia is characterized by dizziness, headache, visual...
Definition of hypertension
A survey of the literature of the past few decades shows that the definition of hypertension has changed drastically, and it seems to continue to change. It is presently recommended that antihypertensive therapy is started in patients who have confirmed hypertension, defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment ofHigh Blood Pressure (JNC 7) as a blood pressure (BP) level exceeding 140 90 mmHg. However, data from the Framingham Heart Study 1 make it exceedingly clear that BP is directly related to cardiovascular events, even at levels below that defined as hypertensive by the JNC 7 2 . High normal BP was associated with a several-fold increase of cardiovascular disease in the Framingham population (Figure 1). A number of recent studies have shown that lowering BP in the so-called normotensive population reduces morbidity and mortality. These recent data indicate that any arbitrary definition of hypertension, such as...
According to two meta-analyses fish oils have a significant but modest effect dose-dependent, on blood pressure in hypertension (Geleijnse et al 2002, Morris et al 1993). The DHA component is likely to have stronger effects than EPA. In contrast, a 2006 Cochrane review found no significant changes to SBP or DBP with n-3 EFA consumption of vegetable or fish origin (Hooper et al 2006). The first meta-analysis was of 31 placebo-controlled trials involving 1356 subjects and detected a statistically significant dose-response effect on blood pressure when studies were grouped by omega-3 fatty acid dose -1.3 -0.7 mmHg at doses
High blood pressure
High blood pressure is when the resting blood pressure is above normal. The World Health Organisation defines high blood pressure as consistently exceeding 160 mmHg systolic and 95 mmHg diastolic. High blood pressure is a common complaint and if serious may result in a stroke or a heart attack, due to the fact that the heart is made to work harder to force blood through the system. Causes of high blood pressure include High blood pressure can be controlled by anti-hypertensive drugs which help to regulate and lower blood pressure
Portal Hypertension
Portal hypertension is frequently a systemic complication of liver cirrhosis, however different pathologies such as obstruction at the post-sinusoidal (e.g. hepatic vein), sinusoidal (e.g. cirrhosis) or pre-sinusoidal (e.g. portal vein) level may also cause portal hypertension 27 . The most common cause of portal hypertension is liver cirrhosis. Associated complications include variceal bleeding, ascites and splenomegaly. A primary consequence of the increased pressure in the portal tract is dilatation of vessels. Later, as a result of the development of porto-systemic shunting, the blood flow to the liver diminishes and the size of the portal vessels is again reduced. Increased porto-systemic shunting results in less effective metabolism of absorbed nutrients and accumulation of toxic metabolites such as ammonia in the blood. This may lead to the clinical manifestations of hepatic encephalopathy. As decreased portal flow correlates with the presence of liver atrophy, porto-systemic...
In the 1970s Yamagami et al observed a deficiency in CoQ10 in patients with hypertension (1975, 1976) and suggested that correction of the deficiency could result in hypertensive effects. Small studies were initially conducted with hypertensive patients identified as CoQ10 deficient. Since then, significant antihypertensive activity has been observed in several clinical studies (Burke et al 2001, Digiesi et al 1994, Langsjoen et al 1994), however, not all have identified the subjects' baseline CoQ10 plasma levels and whether oral administration restored levels to within the normal range. It has been suggested that CoQ10 supplementation is associated with a decrease in total peripheral resistance, possibly because of action as an antagonist of vascular superoxide, either scavenging or suppressing its synthesis (McCarty 1999).
What Is Hypertension
Hypertension, or high blood pressure, is defined as a reading of 140 90 on three consecutive measurements at least six hours apart. The definition varies for pregnant women, where hypertension is defined as 140 90 on two consecutive measurements six hours apart. Consistently high blood pressure causes the heart to work harder than it should and can damage the coronary arteries, the brain, the kidneys, and the eyes. Hypertension is a major cause of stroke. A kidney (left) and a cross-section of a heart (right) that were affected by hypertension. The heart shows signs of advanced atherosclerosis, one possible complication arising from hypertension. Photograph by Dr. E. Walker. Photo Researchers, Inc. Reproduced by permission. A kidney (left) and a cross-section of a heart (right) that were affected by hypertension. The heart shows signs of advanced atherosclerosis, one possible complication arising from hypertension. Photograph by Dr. E. Walker. Photo Researchers, Inc. Reproduced by...
Data from NHANES III show that the age-adjusted prevalence of high blood pressure increases progressively with higher levels of BMI in men and women (Figure 2). 2 High blood pressure is defined as mean systolic blood pressure 140 mm Hg, or mean diastolic blood pressure 90 mm Hg, or currently taking anti-hypertensive medication. The prevalence of high blood pressure in adults with BMI 30 is 38.4 percent for men and 32.2 percent for women, respectively, compared with 18.2 percent for men and 16.5 percent for women with BMI 25, a relative risk of 2.1 and 1.9 for men and women, respectively. The direct and independent association between blood pressure and BMI or weight has been shown in numerous cross-sectional studies 3-5, including the large international study of salt (INTERSALT) carried out in more than 10,000 men and women. 6 INTERSALT reported that a 10 kg (22 lb) higher body weight is associated with 3.0 mm Hg higher systolic and 2.3 mm Hg higher diastolic blood pressure. 6 These...
Hypertensive heart disease coronary artery disease and heart failure
ACE inhibitors, and possibly ARBs, are the best monotherapeutic way to reduce LVH, followed by calcium antagonists, diuretics, and, distinctly less effective, beta-blockers. ACE inhibitors are also a cornerstone in the management of the patient with heart failure and the post-MI patient. ACE inhibitors, and possibly ARBs, are probably the best choice for initial therapy in the patient with hypertensive heart disease. Beta-blockers have morbidity and mortality benefits in the post-MI patient but do not have any primary cardioprotective effects in hypertension. Low-dose beta-blockade is also very useful in patients with heart failure. As shown in the Val-HeFT study, the combination of an ACE inhibitor and an ARB may benefit certain patients with heart failure 45 . Morbidity and mortality benefits of diuretics have never been documented in heart failure. However, as in any other edematous state, diuretics will bring symptomatic relief. Calcium antagonists are useful in the patient with...
Dual RAS blockade Blood pressure
Most BP studies showed a small additional drop in systolic and diastolic pressure when an ARB was added to an ACE inhibitor, and vice versa, regardless of the dose level of the first drug. A thorough systematic review and metaanalysis assessed 14 BP studies in hypertensive patients in which patients were evaluated by 24-hour ambulatory BP monitoring 91 . The authors found that the combination of an ACE inhibitor and an ARB reduced BP by an average of 4 3 mmHg when compared with monotherapy. The incremental fall in BP with dual RAS blockade compared with that seen with monotherapy is certainly only a fraction of what is commonly observed with the addition of either a thiazide or calcium antagonist. In conclusion, the recent ONTARGET study data 94 have shattered the halo of dual RAS blockade not only for hypertension but also for nephroprotec-tion. The meta-analysis of Lakhdar et al. 98 has cast doubts on the safety of dual RAS blockade in patients with left ventricular dysfunction. In...
Betablocker and diuretic combinations
Both beta-blockers and diuretics have been documented to lower BP. The Fifth Report of the JNC, released in 1992, labeled diuretics and beta-blockers as the preferred agents for initial therapy of hypertension. This stand was somewhat softened in 1997 by the JNC VI 39 . Nevertheless, the JNC VI still recommended diuretics and beta-blockers as first-line therapy for uncomplicated hypertension because these were, supposedly, the only two drug classes for which a reduction in morbidity or mortality was shown in hypertension. While this is true for diuretics, it is incorrect for beta-blockers. There is no study in which beta-blockers have been shown to reduce morbidity and mortality in hypertension when compared with placebo. In the large UK Medical Research Council (MRC) study, in patients younger than 65 years of age, diuretics reduced the risk of stroke between two and four times better than beta-blockers, despite an equal fall in BP 40 . One can also estimate from this study that, in...
Pill burden and compliance
Experienced clinicians have long recognized that the patient's compliance with a given treatment regimen depends, to some extent, on its complexity. As a simple rule, the more pills a patient has to take the sicker he or she feels and the lesser the compliance. This is particularly true when the treatment regimen requires dosing several times a day. Fixed combinations, therefore, have a distinct advantage. Putting two or three drugs into the same pill may reduce side effects thus, the patient feels less sick and compliance may be enhanced. Indeed, a meta-analysis of four hypertension studies documented a 24 decreased risk of medication noncompliance with a fixed-drug combination regimen when compared with the same medications taken in two separate pills (Figure 24) 58 . Effect of fixed-dose combination vs free-drug combination on the risk of medication noncompliance in cohort with hypertension Hypertension cohort Figure 24 Effect of fixed-dose combination vs free-drug combination on...
Erectile and orgasmic dysfunction
Long-standing, untreated hypertension is well known to have a negative impact on sexual function and can lead to complete impotence. Unfortunately, antihypertensive drugs still have a bad reputation with regard to erectile function. Some of the older antihypertensive drugs, such as resurpine and guanethidine, have a well-known negative effect on erectile and orgasmic function. Diuretics, beta-blockers, and antiadrenergic drugs, as well as alpha-blockers, diminish erectile function. Failure to ejaculate, or even retrograde ejaculation into the bladder, may occur with some antiadrenergic drugs. In women, diuretics and certain antiadrenergic drugs may interfere with lubrication. Beta-blockers are known to cause orgasmic dysfunction in women and men alike. BP lowering (by any drug) may by itself, at least initially, have a slight negative impact on erectile function. However, the body fairly rapidly adjusts to the lower BP level and, with modern antihypertensive therapy (calcium...
To twofer or not to twofer
The two-for-one therapeutic concept or, namely, to treat two conditions with one drug, is attractive for a variety of reasons among these are a reduction in adverse effects, the number of pills, and cost. Physicians and patients, therefore, like the twofer and use it whenever possible. Unfortunately, the concept of the twofer has never been vigorously tested. Ironclad trials have shown that beta-blockers confer secondary cardioprotection in patients who have suffered an acute MI 26 . However, beta-blockers have no primary cardioprotective effect in hypertension, and there are no studies showing that the reduction of BP by beta-blockers confers any additional benefit in the post-MI patient with hypertension, as would be expected from the fact that two risk factors are modified by one and the same drug. In the post-MI patient, it seems more logical to use a beta-blocker for secondary cardioprotection and to treat hypertension separately by adding another drug class that has been shown...
The nothing worksallergic to everything patient
These patients are also called heart sink patients because the physician's heart sinks whenever they show up in the waiting room. What, perhaps, is most important with patients like this is to try to sort the wheat from the chaff. Thus, a very thorough, detailed history regarding previous medications, duration of use and reasons for discontinuation can often provide an astonishing insight. If a patient who is allergic to everything lists among these allergies a dry cough with certain drugs, or pedal edema with others, the physician has to take the reported adverse events more seriously and try to find a drug that the patient can tolerate. Commonly, the patient is willing to be rechallenged when the options are carefully explained. Using low-dose aspirin, and even iron supplements, can mitigate the cough seen with ACE inhibitors. Consider that some patients may be perfectly willing to continue with the ACE inhibitor, despite the persistence of a low-grade cough. Similarly, a patient...
Dual calcium channel blockade
Occasionally, the combination of a dihydropyridine and a nondihydropy-ridine calcium antagonist may be considered. There is some evidence of an additive effect of this combination and it seems, in general, to be well tolerated 102 . Pedal edema is not aggravated by the addition of a nondihydro-pyridine calcium antagonist to a dihydropyridine agent. The combination may be particularly useful in patients with renal failure and hyperkalemia in whom RAS blockade has become relatively contraindicated. However, it must be emphasized that there are only a very few studies in a small number of patients reporting antihypertensive efficacy. Thus, there is surrogate end point evidence only, and no data indicate that the combination reduces morbidity and mortality.
The I want to do it the natural way patient
Not uncommonly, the physician is challenged by a patient who insists on doing it his or her own natural way. Even though most physicians recognize that this endeavor will be futile, an enthusiastic patient should be encouraged to exercise regularly, lose weight and follow a healthy sodium-restricted diet. The only harm that can come from this is that BP remains elevated and the cardiovascular system of the patient continues to be exposed to a high pressure load. It is therefore important to monitor these patients carefully. In this context, the 24-hour ambulatory BP monitor is very useful and allows you to confront the patient with the before and after BP pattern. Very often, there is little difference between the two, and the evidence suffices to motivate the patient to start antihypertensive therapy. Home BP monitoring is less objective because patients have a tendency to cherry pick good BP readings, record these and then bring them to their physician. A good part of white-coat...
The prothrombotic paradox
Hypertension by definition is a hemodynamic disorder and, as such, exposes the arterial tree to increased pulsatile stress. Paradoxically, however, most major complications of longstanding hypertension (ie, heart attack and strokes) are thrombotic rather than hemorrhagic, referred to as the so-called thrombotic paradox of hypertension. Virchow suggested three components facilitating thrombus formation (Virchow's triad) For thromboembolic events to take place, all the components of Virchow's triad must be fulfilled 70 . In hypertensive individuals, abnormalities in blood flow have been well recognized. Hypertension has also been associated with endothelial damage or dysfunction 71 and a hypercoagulable state 70 . This prothrombotic state could be the result of chronic low-grade inflammation. Chronic shear stress can lead to remodeling of the vascular endothelium, turning it from an anticoagulant into a procoagulant surface. The mechanisms leading to endothelial dysfunction are...
When not to use fixed combination therapy
As attractive as fixed combinations are, and although many patients benefit from them, it should be remembered that not every patient with mild to moderately severe hypertension is a candidate for such therapy. Patients need to be thoroughly informed that they are taking a combination of drugs, such as an ARB and a diuretic, in the same pill. Commonly, the labeling of fixed combinations may be deceptive to patients and physicians. In numerous instances, patients have been given inappropriate medication because the physician was not familiar with the ingredients of a fixed Occasionally, some therapeutic flexibility is lost when a patient is taking a fixed combination drug, and this could be a disadvantage in certain clinical situations. For instance, the need for diuresis may vary a great deal depending on the dietary salt intake. This is particularly true in disease states that are susceptible to sudden unexpected changes such as heart failure or severe coronary artery disease....
Synergism of combination therapy
The most common adverse effect of the dihydropyridine calcium antagonist is pedal edema, which is clearly dose dependent. Pedal edema is seen in about 5 of patients on amlodipine 5 mg, in 25 of patients on amlodipine 10 mg, and in over 80 of patients on amlodipine 20 mg (which is above the FDA-approved dose). Pedal edema is predominantly caused by arteriolar dilatation that increases intracapillary pressure (capillary hypertension) and thereby causes fluid exudation into the interstitium (Figure 20). Any drug that causes venular dilatation may diminish capillary hypertension and decrease pedal edema. Both ACE inhibitors and ARBs are known to have this effect. Thus, unsurprisingly, pedal edema was shown to dissipate when benazepril was added to amlodipine in several well-documented studies (Figure 21). In the Lotrel Gauging Improved Control (LOGIC) trial 55 , patients were included on the basis of pedal edema. After 4 weeks, pedal edema diminished significantly in over 80 of patients...
Direct renin inhibitor and diuretic combinations
There are several reasons why the combination of an ACE inhibitor and an ARB should have some additional effects with regard to both BP and hypertensive target organ disease. Indeed, several small studies have demonstrated an additive effect ofthis combination, not so much on BP, but for microproteinuria and also for hemodynamic features in patients with heart failure. In the Candesartan and Lisinopril Microalbuminuria (CALM) study, for instance, 20 mg of lisinopril was combined with 16 mg of candesartan 49 . This combination led to a further decrease in BP and a further reduction in microproteinuria in patients with diabetes and hypertension. However, we cannot possibly conclude from this and other similar studies that the combination had an additive effect because only relatively small doses of the two drug classes were added to each other. A factorial design study, combining increasing doses of losartan with increasing doses of enalapril in a substantial number of patients, showed...
Betablockers with either ACE inhibitors or ARBs
No fixed combination is available of a beta-blocker with either an ACE inhibitor or an ARB, indicating that there is little interest in developing such a combination. Indeed, there are some reasons to suspect that such a combination may have a distinctly less-than-additive effect on BP this viewpoint is supported by the ALLHAT study 43 . Although beta-blockers have been available for the treatment of hypertension for a number of decades, the mechanism of their antihypertensive effect is still ill understood. To some extent, it seems to be related to a decrease in renin secretion from juxtaglomerular cells. A decrease in renin secretion means that there is less angiotensin I available for conversion to angiotensin II. As a consequence, an ACE inhibitor will have less substrate to work on, which, obviously, would translate into a diminished efficacy. The same reasoning holds true for the ARB, as beta-blockade will diminish the levels of circulating angiotensin II, and so the ARB will...
Calcium antagonist and betablocker combinations
Calcium antagonists can be counteracted by the addition of a beta-blocker. Therefore, the combination of these two drug classes seems useful, not only in hypertension but also in patients with stable coronary disease. Both beta-blockers and dihydropyridine calcium antagonists have benefits in patients with coronary disease the negative effects of the calcium antagonist can be diminished by concomitant beta-blockade. In one morbidity and mortality study, such a combination was shown to be beneficial in patients with coronary heart disease. In contrast to dihydropyridine calcium antagonists, verapamil and diltiazem should not be combined with beta-blockers this is because of additive effects on sinus node and atrioventricular conduction.
Calcium antagonist and diuretic combinations
Calcium antagonists, particularly the dihydropyridines, commonly cause pedal edema. Most physicians' knee jerk response when presented with pedal edema is to add a diuretic. However, the pedal edema seen with the use of calcium antagonists is not caused by salt and water retention, but by intra-capillary hypertension secondary to the diminished arteriolar vasoconstriction with upright posture. Thus, this form of vasodilatory edema responds poorly to diuretic therapy, but very well to blockade of the RAS, either by an ACE inhibitor or an ARB. The fact that no fixed combination of a calcium antagonist and a diuretic is available indicates that pharmaceutical companies seem to be reluctant, for good reason or not, to tackle this issue.
Antiadrenergic and diuretic combinations
Diuretic and antiadrenergic combinations were common a few years ago, but are sparingly used in this day and age. Most contain fairly high doses of diuretics and some have to be given twice a day (Figure 13). Antiadrenergic drugs, such as methyldopa, clonidine, guanabenz, and even reserpine, have a favorable effect on a variety of pathophysiologic findings of hypertensive cardiovascular disease. These drugs reduce LVH, vascular hypertrophy, vascular resistance, and proteinuria, maintain cardiac output, and preserve renal hemodynamics. Even in patients with metabolic syndrome, antiadrenergic drugs exert a favorable effect on abnormal endocrine metabolic findings. In low doses, these drugs are reasonably well tolerated. Unfortunately, at the dose at which their antihypertensive efficacy equals that of other drug classes, their adverse-effect profile often prohibits their use in patients with mild hypertension. The most common adverse effects are fatigue, depression, sexual dysfunction...
Diuretics and diuretic combinations
Fixed combinations of a thiazide diuretic and a potassium-sparing drug are commonly used as initial therapy for the treatment of hypertension. In the USA, there are three such fixed combinations available (Figure 11). Of note, triamterene and amiloride have relatively little diuretic or antihypertensive effect, whereas spironolactone and eplerenone act synergistically on BP. ferred by the decrease in BP. In addition, the risk of sudden death has been shown to rise with increasing doses of thiazide diuretics and to be reduced with the addition of a potassium-sparing compound. In general, fixed diuretic combinations are well tolerated and have remarkably few adverse effects. In combinations containing high doses of ACE inhibitors or ARBs hyperkalemia is of concern in susceptible patients, such as patients with diabetes or chronic renal failure. In rare instances, triamterene has been associated with kidney stones. Spironolactone is known to cause gynecomastia, impotence, menstrual...
Evidencebased versus eminencebased therapy
Eminence-based therapy can be defined as making the same mistakes with increasing confidence over an impressive number of years 36 . Numerous prospective, randomized large trials have taught us what is now defined as evidence-based medicine (EBM) in the treatment of hypertension. However, a critical analysis of these trials remains extremely important because they provide the results that should be translated into clinical practice. For instance, the SHEP program 18 is commonly used as EBM for the safety and efficacy of diuretics in patients with isolated systolic hypertension. Before applying this evidence to an individual patient, however, the physician should remember that out of 100 screened patients with isolated systolic hypertension only one was included in the SHEP study and 99 were excluded for one reason or another. Can the evidence derived from 1 of the population be extrapolated to the remaining 99 The application of published inclusion criteria from 13 randomized clinical...
Blood pressure lowering in normotensive patients
The Framingham study has clearly documented that, even within the normo-tensive range, patients with higher BPs have a higher risk of cardiovascular morbidity than those who have an optimal BP 1 . This raises the question of whether one should consider antihypertensive therapy in normotensive patients. Indeed, several studies have shown that lowering BP in the so-called normotensive population reduces cardiovascular morbidity and mortality. This is particularly true for stroke but less so for coronary heart disease. Although it has been accepted that lipid lowering in high-risk patients is beneficial regardless of lipid levels, the same principle is still somewhat foreign with regard to antihypertensive therapy. In my opinion, some normotensive patients at high cardiovascular risk may benefit from antihypertensive therapy. In fact, the benefits of antihypertensive therapy in these normotensive patients will probably exceed those seen in mildly hypertensive patients without any...
How aggressively should blood pressure be lowered
The VALUE study clearly established that patients whose BP was under control after 6 months had a much lower risk of heart attack and stroke than did patients whose BP remained elevated 32 . This appears to indicate that swift BP control should be achieved and argues against the old dictum of start low, go slow. It should be considered, however, that in the VALUE study most patients were taken off multiple drugs and were put on monotherapy (ie, valsartan 80 mg) for several months. Clearly, this is not the way a practicing physician would treat patients. In most placebo-controlled antihypertensive trials, the Kaplan-Meier curves of morbidity and mortality grow apart after 6 months to 1 year. It seems reasonable to treat elevated BP aggressively in a younger patient whose cardiovascular system can tolerate an abrupt decrease in BP. In such a patient, antihypertensive therapy may be initiated with two drugs, such as an ARB and a diuretic, or a calcium antagonist and an ACE inhibitor....
When initial therapy is insufficient To uptitrate to substitute or to combine
One of the most common questions practicing physicians face after starting a patient on treatment with a given antihypertensive drug is how to proceed when BP remains elevated. That physicians are uneasy with this question is illustrated by the fact that patients are often treated for years with the same dose of the same drug or combination, despite the fact that BP is not at goal. Any excuses volunteered by the patient (ie, crowded parking garage, mother-in-law visiting) seem good enough to rationalize that day's high BP as an exception and delay further therapeutic intervention.
Adverse effects and tolerability
Most antihypertensive drugs have some adverse effects that can affect tolerability. For instance, the main adverse effect of dihydropyridine calcium antagonists is pedal edema 23 , which is dose dependent and more common in women than in men. In an overweight, middle-aged woman, calcium antagonist monotherapy will almost invariably trigger, or aggravate, pedal edema and make the patient unhappy with the selection of the initial antihypertensive drug. Of note, not all dihydropyridine calcium antagonists have an equal effect with regard to pedal edema. For a given fall in BP, lercanidipine, manidipine and lacidipine elicit less edema than do amlodipine and nifedipine. The great majority of patients with mild hypertension cannot be controlled with monotherapy, but need two or more drugs to lower BP into the target range. Monotherapy rarely lowers BP sufficiently, because it invariably triggers compensatory mechanisms that serve to maintain BP at its usual pretreat-ment level. Treatment...
Drug therapy or lifestyle modification
The lifestyle modifications recommended by the JNC 7 were mostly nutritional, consisting of weight loss in the overweight, lowering of dietary sodium intake to less than 100 mmol day, modification of alcohol intake to, at most, two drinks per day, and maintenance of an adequate dietary intake of potassium, calcium, and magnesium 2 . The JNC 7 also recommended regular physical activity for all patients with hypertension who have no conditions that would make exercise contraindicated. There is little doubt that many lifestyle factors, such as dietary salt, alcohol intake, lack of exercise, and stress, can affect BP and contribute to hypertension. Conversely, it has been well documented that BP can be lowered by modifying lifestyle. The antihypertensive efficacy oflifestyle modification in four thorough meta-analyses ofa large number ofpatients has been reported 8-11 . Although the fall in BP may appear relatively small, it should not be forgotten that, in contrast to drug therapy,...
Metabolic syndrome and newonset diabetes
The prevalence of obesity, the metabolic syndrome, and frank diabetes has doubled in the USA over the past decade. With more than 60 of adults and 30 of children classified as overweight or obese, the USA has become the fattest nation on earth. Approximately half of all overweight individuals have insulin resistance and 25 of the population of the USA has multiple risk factors for cardiovascular disease. Cardiovascular risk factors tend to cluster, and insulin resistance or diabetes, obesity, and hypertension are common in the same patient. Ever since the pioneering observation of Colin Dollery's team 59,60 more than 20 years ago, a variety of studies have documented that long-term diuretic therapy, particularly when combined with a beta-blocker, diminishes glucose tolerance and increases the risk of new-onset diabetes. Conversely, as has been revealed in more recent trials, treatment with antihypertensive drugs, such as blockers of the RAS or calcium antagonists, appears to decrease...
Outcome trials
The ASCOT study further attests to the benefit ofthe combination of an ACE inhibitor with a dihydropyridine calcium antagonist 54 . ASCOT was designed to compare the effect of the standard antihypertensive regimen (a beta-blocker and a diuretic) with that of a more contemporary regimen (calcium antagonist and an ACE inhibitor) on coronary artery disease. In the randomized, double-blind Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, 11,506 patients with hypertension who were at high risk for cardiovascular events were randomized to either benazepril plus amlodipine or benazepril plus HCTZ 57 . The study was terminated early because there was a significant 20 reduction in primary outcome events (cardiovascular death, nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization) in the benazepril amlodipine arm when compared with the...
Combination therapy
Cardiovascular risk factors, such as hypertension, diabetes, and hyperlipidemia, as well as cardiovascular disease states, such as coronary heart disease, heart failure, and certain arrhythmias, are amenable to a variety of therapeutic interventions that have been proven to be beneficial. However, the combination ofthese interventions has rarely been studied in a rigorous scientific way. No data are available that analyze the relevant contribution of each drug to the overall outcome in a given patient. Progress has been made in identifying and understanding some drug interactions, allowing the rational combination of certain drugs in a given patient. Drug combinations may be rational for several reasons (Figure 10) Drug A is effective but has an adverse effect or elicits a risk that can be antagonized or abolished by Drug B Drug B may or may not have an effect on a surrogate end point. A classic example of this scenario is the use of a potassium-sparing diuretic, such as triamterene,...
Stepdown therapy
Should the patient be successful in modifying their lifestyle weeks or months after BP is controlled with antihypertensive therapy, it is reasonable to consider using the step-down approach to decrease the dose, or number, of antihypertensive drugs taken, or even to stop therapy completely. Lowering BP over the long term by using antihypertensive drugs such as ACE inhibitors, ARBs and calcium antagonists, will reduce vascular hypertrophy and target organ disease and will restore endothelial function. After antihypertensive therapy is stopped in a successfully treated patient, it is often possible for that patient to stay off therapy for months, even years, provided that they maintain reasonable lifestyle modifications and monitor their BP regularly 16 . Again, lifestyle modification should not be considered as a substitute for drug therapy in hypertension, but rather should be complementary to drug therapy.
Uptitration of the original drug to double the dosage is reasonable only if distinctly enhanced antihypertensive efficacy has been documented and the cost is not prohibitive. Most antihypertensive drugs have a rather shallow dose-response curve and increasing the dose has little additional effect on BP. For instance, doubling the starting dose oflosartan from 50 mg to 100 mg, has not been shown to increase antihypertensive efficacy. In a situation like this, it is more rational to combine a low dose of a diuretic with the ARB. Indeed, the combination has been shown to lower BP better than a higher dose of losartan monotherapy 29 . In contrast, additional antihypertensive efficacy can be gained using amlodipine when the starting dose is doubled from 5 mg to 10 mg furthermore, the cost of the 10 mg dose is less than that of two 5 mg doses. However, the incidence of pedal edema also increases with the higher dose of amlodipine. Pedal edema is a well-known, dose-dependent side effect...
Alcohol abuse
It stimulates the sympathetic nervous system, as well as the RAS, and may cause thirst and dehydration, which often are counteracted by excessive salt and water retention. Chronic alcohol abuse is not an uncommon cause of seemingly refractory hypertension. Calcium antagonists are the most efficient first-line therapy in the alcoholic hypertensive patient. If combination therapy is needed, a beta-blocker could be useful because it diminishes the activity of the sympathetic nervous system. ACE inhibitors are somewhat less efficacious because of alcohol-associated fluctuations in fluid volume state. Diuretics are often relatively contraindicated because they may trigger an attack of gout in susceptible patients. Not uncommonly, allopuritol or febroxustat may have given to control hyperuricemix before diuretic therapy can be initiated.
Black patients
Hypertension is more common in black than in white patients, and its course is distinctly more severe. Black patients have a three-times higher mortality rate from cardiovascular disease than do white patients, and their risk of end-stage renal disease is several times greater. These simple facts indicate that cardiovascular diseases, such as hypertension, hyperlipidemia, and diabetes, should be treated most aggressively in the black population. However, the impediments to aggressive therapy in this population are numerous and range from relative inefficacy of certain antihypertensive drug classes and ill-perceived adverse effects, to socioeconomic factors. No racial difference in antihypertensive efficacy has been documented for calcium antagonists and diuretics. In a meta-analysis, calcium antagonists were the only drug class showing efficacy in all BP strata 85 . In contrast, ACE inhibitors and ARBs, at a given dose, have distinctly less effect on BP in black patients than in white...
In the patient with diabetic hypertensive renal disease, blockade of the RAS has been shown to be nephroprotective that is, to diminish proteinuria and slow down the decline in renal function. In type 1 diabetes, most proteinuria studies have used ACE inhibitors, whereas, for type 2 diabetes, ARBs have mostly been used. However, the American Diabetes Association (ADA) have concluded that the evidence was sufficient to state that both drug classes, ACE inhibitors and ARBs, are indicated for nephroprotection in susceptible patients. Although neither ACE inhibitors nor ARBs are labeled for use to decrease proteinuria albuminuria or to exert any nephroprotective effect, some studies show that nondihydropyridine calcium antagonists, such as diltiazem and verapamil, reduce urinary protein excretion more than the dihydropyridines, specifically nifedipine. A systematic review by Bakris et al. showed a significantly greater reduction of proteinuria with the nondihydropyridine derivatives than...
Dementia is a major concern in the elderly hypertensive patient. Patients with hypertension have been shown to suffer cognitive dysfunction and dementia of all types more commonly than do normotensive subjects. The effects of antihypertensive therapy on dementia are not well documented. However, provocative findings from the Syst-Eur trial have shown that dihydropyridine calcium antagonists reduce dementia by as much as 55 (Figure 29) 69 . In some, but not all, studies, statins also showed a beneficial effect on dementia. Although this remains to be confirmed, it nevertheless makes calcium antagonists, possibly in combination with a statin, an attractive choice for the elderly patient. More recently ARBs and lipophilic ACE inhibitors have also been reported to reduce the risk of dementia. Figure 29 Syst-Eur Effect of calcium antagonist treatment on dementia. Syst-Eur, Systolic Hypertension in Europe. Reproduced from Forette etal. 69 . Figure 29 Syst-Eur Effect of calcium antagonist...
The effects of antihypertensive agents on lipids Antihypertensive agent Figure 28 The effects of antihypertensive agents on lipids. increase decrease , uncertain ACE, angiotensin-converting inhibitor HDL, high-density lipoprotein component NC, no change TC, total cholesterol TG, triglyceride. Adapted from Cohn etal. 45 . Figure 28 The effects of antihypertensive agents on lipids. increase decrease , uncertain ACE, angiotensin-converting inhibitor HDL, high-density lipoprotein component NC, no change TC, total cholesterol TG, triglyceride. Adapted from Cohn etal. 45 .
Atrial fibrillation
Atrial fibrillation is an under-recognized complication of long-standing hypertension and increases the likelihood of morbidity and mortality - at least doubling the risk for cardiovascular death or stroke. The main factors predicting development of atrial fibrillation are age, male sex, severity of hypertension, obesity, and presence of LVH on electrocardiogram. Some findings suggest that the choice of BP-lowering treatment could reduce the risk of developing atrial fibrillation. Notably, treatment that inhibits the RAS might be more likely to prevent new-onset atrial fibrillation than other antihypertensitive drug classes. The mechanism for this benefit is unclear but could be, at least in part, dependent on favorable structural regression of left ventricular mass and a reduction in left atrial size.
Drug interactions
Drug-drug interactions have become increasingly important over the past few decades because, in most cases, two or more drugs are needed to get BP to goal, and also because hypertension is rarely an isolated disorder and concomitant risk factors or diseases may require multiple drugs that can, potentially, interact with a given antihypertensive agent. It is almost impossible for the practicing physician to remember all potential interactions, some of which can lead to severe and even fatal adverse events. Fortunately, computer programs, such as Epocrates , have become very useful in identifying the most important interactions. Of particular interest is the long list of drugs or agents that interfere with the cytochrome P450 system. An example of such an agent is grapefruit juice, which has been shown to increase plasma concentration of certain calcium antagonists and statins. All other factors being equal (which they rarely are), the practicing physician is advised to preferentially...
Substituting a different antihypertensive drug should be considered if there is no antihypertensive efficacy with a reasonable dose, as is occasionally seen with beta-blockers, ACE inhibitors or ARBs in black patients, or if there are intolerable side effects, such as angioedema. Fortunately, most modern antihypertensive drugs are well tolerated and serious adverse effects are few. Some patients are even willing to put up with a scratchy throat or low-grade cough associated with ACE inhibitors, or the pedal edema associated with calcium antagonists, once they know that these are harmless conditions related to the drugs.
The drug class best documented to reduce morbidity and mortality in hypertension, when compared with either placebo or active therapy, remains the thiazide diuretics, specifically chlorthalidone. In all diuretic-based trials, other antihypertensive drug classes, such as beta-blockers and antiadrenergics, have been added to titrate BP to target. However, although the addition of these drugs to diuretic therapy adds to the antihypertensive efficacy (and therefore, seemingly has a beneficial effect on the surrogate end point), they have not been shown to enhance the benefit of diuretics on morbidity and mortality (the real end point). Thus, it cannot be concluded that the addition of these drugs is beneficial. Even shakier is the conclusion that these drugs by themselves (when not added to diuretics) will be beneficial. In contrast to chlorthalidone therapy, treating hypertension with beta-blockers, for instance, has not been shown to offer any primary cardioprotective or...
Lowsalt diet
Lifestyle modifications can profoundly affect antihypertensive therapy for instance, a low sodium diet will decrease potassium excretion in a patient who is on a diuretic, as less sodium is available at the level of the distal tubule for exchange against potassium. Thus, a low-sodium diet will prevent total body potassium depletion and, thereby, may enhance the morbidity and mortality benefits of diuretic therapy. In the Systolic Hypertension in the Elderly (SHEP) study 12 , patients who had hypokalemia showed no reduction in heart attacks and strokes when compared with patients whose potassium was normal, despite a similar fall in BP. In addition, by stimulating the renin-angiotensin-aldosterone system (RAS), a low-sodium diet also enhances the antihypertensive efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Not only is BP lowered more efficiently with ACE inhibitors and ARBs in a patient on a low-sodium diet, but also the...
The J curve
Much ink has been expended on whether the relationship between BP and cardiovascular morbidity and mortality follows a J-shaped pattern. Conceivably, as BP is lowered, morbidity and mortality diminish, but, clearly, there is a point at which further lowering leads to the under-perfusion of vital organs and, thereby, will increase morbidity and mortality. Thus, it stands to reason that a J curve has to exist. However, it is not so clear whether the nadir of the J curve is anywhere near the target range of the systolic or diastolic pressure. Most studies have shown that for both cerebrovascular and renal disease there seems to be no J-shaped curve with regard to systolic or diastolic pressure. However, numerous studies have shown that the issue is different for diastolic pressure and coronary artery disease. The myocardium is perfused almost exclusively during diastole and, therefore, diastolic pressure is critically important for coronary perfusion. Most studies that have examined the...
The unique efficacy of dryneedling acupuncture in sports medicine
Some athletes resort to drugs to achieve better performance, and they risk paying a high price for this in the future. Anabolic steroids greatly increase the risk of cardiovascular damage, heart attack, and stroke, because they cause hypertension, a decrease in high-density blood lipoproteins, and an increase in low-density lipoproteins. The consumption of male sex hormones by male athletes can decrease testicular function, causing both lowered sperm formation and a reduction in the natural secretion of testosterone. The use of amphetamines and cocaine
Indications Horseradish
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Effects on Sleep Quality
Sleep disturbance is common among patients with chronic bronchitis and asthma. Sleep disturbance in children with asthma is associated with psychological problems and impairment of memory (59). Among patients with COPD, 41 reported at least one symptom of disturbed sleep (60), possibly contributing to nocturnal oxygen desaturation, the development of pulmonary hypertension, polycythemia, and cardiac arrhythmias (61,62). A randomized double-blinded study involving 36 patients with moderate to severe COPD showed that ipratropium increased total sleep time, decreased the severity of nocturnal desaturation, and improved the patient's perceptions of sleep quality (63).
The Nutritional Transition and Its Health Effects
With people living longer, and with low birth weight at an all-time low, Asian health should be improving. But with increased Westernization of the Asian diet, elevated tobacco use (generally among Asian men), and lifestyle changes (such as decreased physical activity), there has been a marked rise in cardiovascular disease (CVD), diabetes mellitus, hypertension (high blood pressure), and certain cancers. obesity is also a growing health problem in Asia, and is strongly associated with hypertension (along with body mass index and age). Despite the low obesity levels in the Asia Pacific region, rates of obesity-related diseases such as diabetes and CVD are on the rise. High blood pressure is also a growing problem in Asia. In India, Indonesia, and Thailand alone, nearly 10 to 15 percent of adults have high blood pressure. Hypertension is dangerous because it increases a person's risk of developing CVD or having a stroke.
Presentday Cultivation And Usage
Today, carob trees are grown for reforestation in the poor soils and dry environments of the coastal areas of some Mediterranean regions. The traditional uses of the carob bean (pod) until the 1960s were of the pulp (90 of the fruit) for animal feeding, or as a chocolate or cocoa substitute. Unlike cocoa, carob does not contain caffeine or theobromine. People who are allergic to chocolate can generally eat carob without a problem. It is also low in sodium and high in potassium, making it desirable for diets used to treat congestive heart failure and hypertension (Yousif & Alghzawi, 2000). In Europe, the part of the fruit that currently has the
Causes of Autism Spectrum Disorders
Lauren's mother had had an extremely difficult pregnancy. She had high blood pressure and was placed on total bed rest for 6 weeks. Her amniotic fluid levels were low and the baby rarely moved. Her doctor was worried about fetal distress, and induced labor with Pitocin a month early. Lauren was born weighing only 5 pounds. She required resuscitation at birth and remained hospitalized, on oxygen, for 2 weeks. Could these complications really be just a coincidence or were they related to Lauren's difficulties
General Treatment of Dementia
And medications with CNS effects (sedatives, narcotics, antidepressants, anxiolytics, and antihistamines) should be discontinued, or used sparingly. The clinician should also be aware that other commonly prescribed medications, including antiemetics, antispasmodics for the bladder, H2 receptor antagonists, antiarrhythmic agents, antihypertensive agents, and nonsteroidal anti-inflammatory agents, may also cause cognitive impairment.
SHR and Wistar Kyoto rats
Just as the F344 and LEW rats have become the 'golden standards' for strain differences in the HPA axis, the SHR and the Wistar Kyoto rats have become the standards for strain differences in blood pressure. As mentioned above, the SHR strain was developed by selectively inbreeding Wistar Kyoto rats with spontaneous high blood pressure (Okamoto and Aoki, 1963). Though SHR are born with a relatively normal blood pressure, after 5-6 weeks the pressure starts to rise slowly to reach systolic levels of 180-200 mmHg. The animals also develop many features of hypertensive end-organ damage, including cardiac hypertrophy, cardiac failure and renal dysfunction (Pinto et al, 1998). It has been shown that SHR indeed have an increased vasomotor control, presumably due to an increased a-sympathetic activity (Eyal et al, 1997). Interestingly, this hyperactivity of the sympathetic nervous system is already seen prior to the development of overt hypertension. Although SHR have higher blood pressure...
Statistical Assessment of Validity
There are two broad approaches to establishing validity between test and reference measures comparison of mean values and correlation. The use of mean values is appropriate where group intakes are to be determined or where an absolute measure of intake is required. This is especially important where a threshold value of intake will be used to make recommendations (e.g., recommending an increase in potassium intake because of its association with lower blood pressure and reduced risk of myocardial infarction there would be no point in recommending additional consumption of potassium for individuals who were identified as having intakes already above the levels that were seen to be protective). The correlation technique (plotting the observed measure against the reference measure) is appropriate where it is important to classify subjects according to high or low intakes because differences in intake are associated with different levels of disease risk. In relation to disease risk, a...
Female Reproductive System Disorders
Oedema and hypertension during pregnancy In a partially double-blind, placebo-controlled clinical trial, a combination of EPO, fish oil and magnesium oxide was found to be superior to placebo in lowering the incidence of oedema (P 0.004) in pregnant women. Significantly fewer women developed hypertension in the group receiving the oils and magnesium oxide. The three cases of eclampsia all occurred in the control group (D'Almeida et al 1992).
Cardiovascular Diseases
Hypertension A double-blind, placebo-controlled study with a crossover design found that the combination of EPO and fish oils significantly lowered blood pressure in 25 non-obese black patients with mild-moderate uncomplicated essential hypertension after 8-12 weeks compared with placebo (sunflower and linseed oil) (Venter et al 1988). Other smaller studies have found a similar beneficial effect in hypertensive patients. A combination of 4 g GLA and DHA daily for 6 weeks reduced blood pressure in nine mildly hypertensive patients compared with placebo (sunflower oil) (Deferne & Leeds 1992).
Selection of Treatment for Specific Patients
Available resources Clinicians trained in the use of psychosocial treatments for eating disorders are likely to be found in most metropolitan areas but may not be available in smaller cities or rural areas. Insurance companies vary in coverage for treatment of eating disorders, and some insurance plans may pay for obesity treatment only if there is a clear medical indication (e.g., hypertension or other cardiovascular risk). Thus, treatment decisions may need to take into account pragmatic factors, such as clinician availability and training or patient insurance plan coverage. Self-help programs may be appropriate for carefully screened, motivated patients with mild to moderate binge eating. However, comorbid psychopathology and high-frequency binge eating may require more intensive clinical intervention.
Cardiovascular Effects
Some of the flavonol glycosides and flavonoids isolated from the genus are pharmacologically effective in dilation of the coronary artery, inhibition of platelet aggregation, and delayed formation of thrombi (8). Chen et al. (49) described the isolation of five new prenyflavones, yinyanghuo A, B, C, D, and E. Yingyanghuo A and B were shown to have significant antiplatelet activity. Flavone glycosides of E. koreanum (TFG) stimulated murine macrophages. The fibrinolytic activity of stimulated macrophages was approximately 2.8-fold that of the controls. In vivo experiments reported that the effect of TFG on spontaneously hypertensive and apoplexic rats was very evident. The abiotic rate of TFG-stimulated rats was 5 , while that of the control group was 90 (50). Epimedium may help to dilate the coronary vessels, increasing coronary blood flow by reducing vascular resistance (51). E. decoctum and its extracts give certain protection in the myocardial ischemia of rat caused by pituitrin. In...
Success friendship and dominance
As a final example of a social motive, we all vary with respect to our liking for power. This is concerned with wanting to be dominant and or to be recognised as of high status or good repute. Those with a high need for power tend to have high blood pressure and high catecholamine levels, which means that they are relatively argumentative, tend to be angry, play much sport and have trouble sleeping. Of course, as well as there being large variation in the need for power, there is a similarly large variation in how people use whatever power they might have. At one extreme are social goals and at the other personal ambition and aggrandisement very different styles of leadership might result.
Lung Involvement in SLE
Pulmonary hemorrhage, or bleeding in the lungs, is a very serious complication of SLE. It is the result of chronic irritation of the blood vessels in the lungs. For oxygen to be moved from the air breathed into the lungs to the blood vessels in the lungs, the blood vessels must be very close to the surface of the alveoli, or air sacs. If the blood vessels are very irritated by inflammation, they may begin leaking blood into the alveoli. This prevents the proper exchange of oxygen. Poor heart function will make this worse, because it results in increased blood pressure in the lungs (pulmonary hypertension), which leads to increased bleeding. If a child is coughing up blood, he or she should be taken to the physician immediately often a small amount of blood is coming from irritation in the airway or from blood swallowed because of a cut in the nose or mouth, but it is best to make sure. If a child really is bleeding inside the lung, there is no time
BPharmacotherapy Trials
The diet plus placebo group. 386, 390-393, 395 However, one study on dexfenfluramine 394 showed increased blood pressure compared to controls, even though weight loss was greater with dexfen-fluramine than with placebo. Another study showed blood pressure lowering consistent with weight reduction produced by dexfenfluramine in women with upper-body obesity, but not in women with lower-body obesity. 387 In a combined summary of data on orlistat presented at the FDA Endocrinologic and Metabolic Drugs Advisory Committee Meeting (held in Bethesda, Maryland, in May 1997), only a small decrease in systolic (approximately 2 mm Hg) and dias-tolic (approximately 1 mm Hg) blood pressure was observed compared to the placebo. 388 In a study of sibutramine, a net weight loss at 3 months of approximately 2 kg (4.4 lb) did not result in lower blood pressure compared with placebo controls. 389 Eleven double-blind placebo-controlled trials lasting from 12 to 52 weeks showed that sibutramine is...
Smallvessel Occlusion
Small-vessel occlusions, i.e., thrombosis of a single perforating cerebral artery, cause lacunar ischemic strokes. A lacunar infarct usually occurs in the internal capsule or thalamus and presents clinically as a pure motor stroke, pure sensory stroke, sensomotor stroke, dysarthria clumsy hand or ataxic hemiparesis. Patients with typical lacunar infarct syndromes account for approximately 20 of all ischemic strokes, and hypertensive small-vessel disease seems to be the most important etiology 29 , Because heavy drinking of alcohol is a frequent cause of arterial hypertension, it is assumed to associate with small-vessel occlusion as well. However, conflicting observations have also been reported. Some studies have not shown alcohol to be a significant risk factor 29-31 , whereas others have 9,32 , The study ofYou et al. included a rather large series of young adults with lacunar infarcts 33 . This study suggested that long-term heavy alcohol consumption is a risk factor for ischemic...
Cardiovascular Disease
Cardiovascular disease (CVD), and the resulting complications, is the main cause of death for both males and females in the United States and other technologically advanced countries of the world. It usually is in the top five causes of death in lesser-developed countries. Diseases of the cardiovascular system include those that compromise the pumping ability of the heart, cause failure of the valves, or result in narrowing or hardening of the arteries. In addition, toxins and infectious agents may damage the heart and blood vessels. Injury or failure of the cardiovascular system, especially the heart, also will affect the peripheral tissues that depend on the delivery of nutrients and the removal of wastes through the blood vascular system. CVD is a family of diseases that includes hypertension, atherosclerosis, coronary heart disease, and stroke.
Risks With Stopping Medications
Thinking about stopping the use of medications, or even actually stopping, is very common. It's something most people go through even when taking nonpsychiatric drugs, such as medication for high blood pressure. Research has shown that seven out of every ten people with bipolar disorder stop taking their medication at some point, and nine out of every ten seriously consider discontinuing medication treatment (Colom and Vieta 2006). Unfortunately, stopping medication often results in another mood episode, usually within the next six months to one year, and also increases the risk of suicide attempts (Tondo and Baldessarini 2000).
Table 78 Exercise Adaptations for Medical Problems
Hypertension (High Blood Pressure) Strengthening is best done using a lower load and more repetitions. A person with hypertension should avoid isometric exercises (which involve a sustained muscle contraction rather than moving the muscle through its range of motion such as in a biceps curl ).
Coronary Artery Disease
Coronary artery disease (CAD) refers to any of the conditions that affect the coronary arteries and reduces blood flow and nutrients to the heart. It is the leading cause of death worldwide for both men and women. Atherosclerosis is the primary cause of CAD. Controlled risk factors associated with CAD include hypertension, cigarette smoking, elevated blood lipids (e.g., cholesterol, triglyceride), a high-fat diet (especially saturated fats and trans-fatty acids), physical inactivity, obesity, diabetes, and stress. Lifestyle changes can assist in prevention of CAD. Uncontrolled risk factors include a family history of CAD, gender (higher in males), and increasing age.
Adults Ages 19 Years and Older Methods Used to Set the AI
Although the preponderance of the data shows a protective effect of consumption of high fiber and high fiber-containing foods against CHD (see earlier section, Dietary Fiber, Functional Fiber, and the Prevention of Hyperlipidemia, Hypertension, and Coronary Heart Disease ), there are exceptions to these findings. A more important consideration for establishing a requirement for fiber is the fact that the dietary intake data from epidemiological studies are on fiber-containing foods, which are considered Dietary Fiber. Certain investigators specifically analyzed diets for Dietary Fiber (Burr and Sweetnam, 1982 Hallfrisch et al., 1988 Khaw and Barrett-Connor, 1987 Kromhout et al., 1982 Kushi et al., 1985 Morris et al., 1977 Pietinen et al., 1996 Rimm et al., 1996), but others used indicators of Dietary Fiber intake such as cereals, vegetables, fruits, whole grains, or legumes. There are many constituents of whole grains, in addition to Dietary Fiber, that...
Metabolism Of Thiamin
Thiamin that is not bound to plasma proteins is rapidly filtered at the glomerulus. Diuresis increases the excretion of the vitamin, and patients who are treated with diuretics are potentially at risk of thiamin deficiency. Some of the diuretics used in the treatment of hypertension may also inhibit cardiac (and other tissue) uptake of thiamin, thus further impairing thiamin status, which may be a factor in the etiology of heart failure (Suter and Vetter, 2000).
Contraindications And Precautions
Some authors suggest that high-dose Siberian ginseng should be avoided by those with cardiovascular disease or hypertension (BP 80 90 mmHg) (Mahady et al 2000). Others merely suggest a caution, as reports are largely unsubstantiated (Holford & 2007 Elsevier Australia Cass 2001). As such, it is recommended that people with hypertension should be monitored if using high doses. A study in elderly people with hypertension over 8 weeks did not affect blood pressure control (Cicero et al 2004). It is not recommended for use in pregnancy and people with hypertension should be monitored if using high doses. It should not be used In pregnancy and high doses should be used with care by those with hypertension.
Applications To Health Promotion And Disease Prevention
Long-chain EPA and DHA are potent anti-arrhythmic agents that help to improve the vascular endothelial function and to lower blood pressure, platelet sensitivity, and serum triglyceride levels. Dietary ALA consumed as flax seed oil was shown to raise serum n-3 PUFAs, such as EPA and DHA levels (Mantzioris et al., 1994 Cunnane et al., 1995). In a recent report, intake of flax seed oil and milled flax seed for 4 weeks resulted in significant increases in plasma ALA levels (Dupasquier et al., 2006 Austria et al., 2008) and aortic tissue. Flax seed supplementation was also reported to reduce the n-6 to n-3 PUFA ratio, primarily as a result of the elevated levels of circulating n-3 PUFAs (Dupasquier et al., 2006).
Traditional Low Purine Diet
Many patients with gout are overweight, and a combination of caloric reduction and exercise can have a beneficial impact on any associated hypertension, hyperlipidemia, and insulin resistance syndrome via enhanced renal excretion of urate and reduced serum urate levels. However, although weight reduction, purine restriction, and reduced alcohol consumption may transiently reduce serum urate, there are no long-term studies demonstrating the efficacy of such an approach. Any benefit that does occur is likely to be small, and any limited reduction in serum urate levels
Ethanol And Smooth Muscle Cell Proliferation
Excessive proliferation of arterial SMC plays an important role in the process of atherogenesis and hypertension 14 , Therefore, inhibition and stimulation of VSMC proliferation may be crucial for preventing and exacerbating, respectively, the development of cardiovascular disease. One key regulatory enzyme pathway for control points within the cell cycle has been identified as mitogen-activated protein kinases (MAPKs) 51 , They are serine threonine protein kinases that are activated by dual phosphorylation ofboth tyrosine and threonine residues. Highly conserved during eukaryotic evolution, they are rapidly activated in response to ligand binding by both growth factor receptors with intrinsic tyrosine kinase activity, such as the platelet derived growth factor (PDGF) receptor, and receptors that are coupled to G-proteins such as the thrombin receptor 51-53 , They are also activated by hemodynamic stimuli 11 . Members of the MAPK family include the ERKs (ERK-1 and and stimulation of...
General Pharmacological Studies
Hypertension The flavonoids of chrysanthemum have been shown to increase blood circulation in experimental animals, suggesting a potential role in reducing hypertension. Several fractions from the ethanol extract also showed significant anti-myocardial ischemia and antiarrhythmia activities in rats (2).
Biological Effects Of A Paniculata
A. paniculata has been reported to have multiple pharmacological activities, including the lowering of blood pressure. Anecdotally, it is taken as a bitter infusion from six to seven leaves for lowering very high blood pressure. A published report by Ahmad and Asmawi (12) indicated that the extract of this plant was used among Malays in Malaysia for the treatment of hypertension. Wang and Zhao (13) reported that the extract could alleviate atherosclerotic artery stenosis induced by both deendothelialization and a high-cholesterol diet. This chapter reviews the authors' investigations into the cardiovascular effects of a crude water extract of A. paniculata, its semipurified fractions, and some of its diterpenoid compounds. Suryaprabha et al. (15) reported that in hypertensive states, there is an increased amount of free radicals. Elevated levels of free radicals have in turn been associated with increased amounts of ACE in the kidneys (16). Free radicals, especially superoxide ions,...
Adverse Effects And Reactions Allergies And Toxicity
In another human case report, drinking 100 g of a harmala seed decoction resulted in unconsciousness, hypertension, tachycardia, and tachyhypnea, and elevation of hepatic and renal function markers. Poisoning with high doses of harmala can be life-threatening, although patients usually recover with supportive therapy alone (Yuruktumen et al., 2008).
Special Populations Children
Elevated blood pressure begins well before adulthood, during the first two decades of life and perhaps earlier during gestation. Numerous observational studies have documented that blood pressure tracks with age from childhood into the adult years. Hence, efforts to reduce blood pressure and to prevent the age-related rise in blood pressure in childhood are prudent. Hypertension during pregnancy is a constellation of diverse clinical conditions, some of which can be extremely serious. Of substantial concern are preeclampsia and eclampsia. Both are multisystem disorders that are manifest by the onset of hypertension and proteinuria during the second half of pregnancy. Convulsions occur in the setting of eclampsia but not preeclampsia. The cause of these disorders is unknown. Several dietary interventions, including salt restriction, fish oil supplementation, and calcium supplementation, have been tested as a means to prevent preeclampsia, but none is considered effective. Although a...
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...


text: Stratford-upon-Avon ( location: 52.19°N -1.71°W ) is a little town in England with a population of 22,576. Stratford-upon-Avon is an important destination on the National Express network. Stratford-upon-Avon has National Express direct inbound connections from 32 towns and cities. Visitors to Stratford-upon-Avon travelling by National Express bus arrive at the main coach station Stratford-upon-Avon Riverside Bus Station. Listed below are typical weekday National Express schedules from 1114 places to Stratford-upon-Avon. If you want the best National Express journeys and cheapest National Express coach tickets but would also like to compare other bus companies? Don't worry! Coachfairer has you covered - just do a search to the place Stratford-upon-Avon, United Kingdom in the form to the right and we'll find all the best journeys and cheapest coach tickets from all operators!

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One long, juicy distraction, this Diddle Stick features a refreshing mix of pink, white and green in watermelon colours, and "I'm Wet" on the shaft.
Approximately 50cm long.
The Diddle Stick is the scene queen here at Pastel Poisons. My first and favourite toy off the press, these bad boys are ready for some fun. Size depends on the individual piece, so please check measurements against the ruler in the pic.
The shorter Diddle Sticks are better for those with less grip strength, or with wrist weakness. The longer ones pack more of a punch. Ultimately, there is something to suit every taste, and custom Diddle sticks are certainly an option.
This item is a hand-illlustrated custom design. Subsequent productions of this item may differ slightly in appearance from the picture above as a result of the creation process. As a hand made item, there are minor imperfections, scuffs and bumps, as pictured. This particular item hasn't been blessed with a hail of glitter, but IS made in a glitter-rich environment.
Please make sure you check out the Toy Care instructions page so you can give your new toy the best treatment possible!
"I'm Wet" Diddle Stick
Postage - Australia and Worldwide
Postage is calculated at a flat rate of $15 Australia-wide, with options for discreet shipping available.
This item is available for postage worldwide at an additional cost. Please contact me directly to arrange shipping outside Australia.


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The Fortaleza family has been making Tequila for four generations, following traditional methods of production. Using agave crushed with stone tahonas, they produce their Still Strength Blanco in copper pot stills, then bottle it without watering it down to a lower proof. It's complex and beautiful, playing vegetal notes of corn, beet and bluegrass off fruitier flavors of green apple skin and papaya, with a hint of campfire in the background. You won't be disappointed just sipping this straight out of the copita.
Spirits Info
Spirits Type: Tequila
Imported by Park Street Imports, Miami, FL
Price: $65
2018 Year's Best
This review appears in the print edtion of the Winter 2018 issue.
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