Home Remedies for Hypertension

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. Blue Heron says that it doesn't matter why you are experiencing high blood pressure, their program will help you permanently lower it in a short amount of time. It does this without side effects, and it only takes about 30 minutes per day. Along with the main program, you also get a bonus called The Natural Blood Pressure Lifestyle Report. This report complements the blood pressure program by helping you understand how high blood pressure occurs, how you can tweak your diet and lower it, different herbal medications that can help, and how your lifestyle can influence your blood pressure in a big way, plus much more. Read more here...

Hypertension Exercise Program Summary


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Project Title Ace Inhibition In Single Ventriclepulmon Hypertension

Summary (provided by applicant) The overall goal of this application is to examine treatment modalities which may improve the clinical care of two groups of patients with congenital heart disease infants born with a single ventricle supplying blood flow to the lungs and body and children with pulmonary hypertension associated with congenital heart disease. The primary hypothesis in infants with single ventricle is that chronic angiotensin converting enzyme (ACE) inhibition favorably modifies the ventricular remodeling response to volume overload and improves ventricular function over the first year of life. Serial changes in ventricular geometry will be assessed using magnetic resonance imaging and compared with measurements of systolic and diastolic function, including the pressure volume relation and the Tei index, and clinical outcome measures including post-operative course and changes in the Ross heart failure classification. The beneficial effect of ACE inhibition is expected to...

Drugs For Systemic Hypertension

Beta blockers are widely used in the management of cardiovascular disorders, including hypertension, angina pectoris, and cardiac arrhythmias. These drugs decrease the heart rate and the cardiac output, decrease blood pressure, and can decrease IOP. Although thiazide-type diuretics are used as initial therapy for most patients with hypertension, beta blockers are commonly used for stage 2 hypertension or other compelling indications.1 Systemic hypertension and glaucoma often coexist in patients, and glaucoma patients frequently use systemic cardiovascular medications.2 Beta-adrenergic blocking drugs for long-term therapy of systemic hypertension are listed in table 9.1. After oral administration of propranolol to ocular hypertensive patients, reduction of IOP occurs within 1 hour, reaching a maximum at 3 hours and lasting at least 7 hours (figure 9.1).8 The reduction of IOP is greater in patients with higher initial measurements compared with lower...

Essential Hypertension

The vast majority of people with hypertension have essential hypertension. An increased total peripheral resistance is a universal characteristic of this condition. Cardiac rate and the cardiac output are elevated in many, but not all, of these cases. The secretion of renin, which is correlated with an-giotensin II production and aldosterone secretion, is likewise variable. Although some people with essential hypertension have low renin secretion, most have either normal or elevated levels of renin secretion. Renin secretion in the normal range is inappropriate for people with hypertension, since high blood pressure should inhibit renin secretion and, through a lowering of aldosterone, result in greater excretion of salt and water. Inappropriately high levels of renin secretion could thus contribute to hypertension by promoting (via stimulation of aldosterone secretion) salt and water retention and high blood volume. Sustained high stress (acting via the sympathetic nervous system)...

Dangers of Hypertension

If other factors remain constant, blood flow increases as arterial blood pressure increases. The organs of people with hypertension are thus adequately perfused with blood until the excessively high pressure causes vascular damage. Because most patients are asymptomatic (without symptoms) until substantial vascular damage has occurred, hypertension is often referred to as a silent killer. Hypertension is dangerous for a number of reasons. First, high arterial pressure increases the afterload, making it more difficult for the ventricles to eject blood. The heart, then, must work harder, which can result in pathological changes in heart structure and function, leading to congestive heart failure. Additionally, high pressure may damage cerebral blood vessels, leading to cerebrovascular accident, or stroke. (Stroke is the third-leading cause of death in the United States.) Finally, hypertension contributes to the development of atherosclerosis, which can itself lead to heart disease and...

Treatment of Hypertension

The first form of treatment that is usually attempted is modification of lifestyle. This modification includes cessation of smoking, moderation of alcohol intake, and weight reduction, if applicable. It can also include programmed exercise and a reduction in sodium intake. People with essential hypertension may have a potassium deficiency, and there is evidence that eating food that is rich in potassium may help to lower blood pressure. There is also evidence that supplementing the diet with Ca2+ may be of benefit, but this is more controversial. If lifestyle modifications alone are insufficient, various drugs may be prescribed. Most commonly, these are diuretics that increase urine volume, thus decreasing blood volume and pressure. Drugs that block Pi-adrenergic receptors (such as atenolol) lower blood pressure by decreasing the cardiac rate and are also frequently prescribed. ACE inhibitors, calcium antagonists, and various vasodilators (table 14.10) may also be used in particular...

HIVassociated Pulmonary Hypertension

Pulmonary hypertension is a severe life-limiting disease, often affecting younger patients. The connection between HIV infection and the development of pulmonary hypertension is well documented (Mette 1992, Simonneau 2004). However, the underlying pathobiology still remains unclear. Given that the prognosis of HIV infection has been improved by HAART, severe pulmonary hypertension is becoming a life-limiting factor (Nunes 2002).

Pulmonary arterial hypertension PAH

1.1 Primary pulmonary hypertension c) Portal hypertension d) HIV-associated pulmonary hypertension Pulmonary hypertension is classified into three clinical stages Latent pulmonary hypertension is characterized when mean pulmonary arterial pressures (PAP) are below 21 mmHg with an exercise-induced increase to values above 30 mmHg. The patients suffer from dyspnea upon exercise. In manifested pulmonary hypertension, the mean PAP exceeds 25 mmHg at rest. Patients already suffer from dyspnea on light exercise. Severe pulmonary hypertension is characterized by a severely reduced cardiac output at rest, which cannot be increased upon exercise, due to the increase in right ventricular afterload. Thus, patients are unable to perform any physical activity without distress.

Genetics of blood pressure and essential hypertension

A number of genome-wide genetic linkage studies of hypertension in affected relative pairs (Caulfield et al., 2003 Kardia et al., 2003 Rao et al., 2003 von Wowern et al., 2003), quantitative levels of blood pressure (de Lange et al., 2004 James et al., 2003) or other study designs have been undertaken in an attempt to localize genes with substantial effects. Candidate gene investigations comparing case control allele frequencies have also been widely applied in studies of hypertension. (e.g. the upper 5 or even better, upper 1 of the blood pressure distribution adjusted for age and sex). Only a few linkage investigations to date could be said to approach these power requirements, notably the British Genetics of Hypertension Study (BRIGHT) (Caulfield et al., 2003) and the NIH HyperGen study (Rao et al., 2003). BRIGHT, which is the largest individual study, comprises more than 2000 affected sibpairs selected to be in the upper 10 5 of the blood pressure distribution. Based on...

Models of Hypertension in Aging

All forms of hypertension studied to date are caused by a defect in the handling of sodium and water by the kidney. There is a shift to the right in the pressure-natriuresis relationship (higher blood pressure) in which a hypertensive individual must increase blood pressure in order to excrete a normal sodium load. There are sex differences in blood pressure control in humans and animals, with males having higher blood pressure than females. However, blood pressure increases in some women after menopause. The mechanisms that play a role in hypertension, and have been studied extensively, include the renin-angiotensin-aldosterone system, endo-thelin, oxidative stress, the sympathetic nervous system, androgen estrogen ratio, and obesity. Rats and mice are commonly used for the study of hypertension and aging. There are both genetic and nongenetic models of hypertension in which the animals exhibit increases in blood pressure spontaneously or are genetically predisposed to increase blood...

Etiology Of Hypertension

Abnormal pressure-natriuresis in hypertension Substantial evidence supports the theory that some form of renal dysfunction plays a role in the development and maintenance of hypertension. A common defect that has been characterized in all forms of hypertension studied to date is a shift in the pressure-natriuresis relationship (Guyton et al., 1972 Hall et al., 1990). The pressure-natriuresis relationship refers to the fact that increased arterial pressure elicits a marked increase in sodium excretion. According to the renal body fluid feedback concept, a long-term increase in arterial pressure or hypertension occurs as a result of a reduction in renal excretory function or a rightward shift in the pressure-natriuresis relationship. In kidneys from normo-tensive individuals, when sodium intake is increased, the blood pressure will increase transiently to increase sodium excretion. When the sodium load has been excreted, the blood pressure returns to normal levels. However, in a...

Genetic Models Of Hypertension

The SHR is a commonly used model of hypertension (Reckelhoff, 2001). These animals develop increases in blood pressure beginning at six to seven weeks of age and reach a stable level of hypertension by 17 to 19 weeks of age. Inhibitors of the renin-angiotensin system reduce blood pressure in SHR, suggesting a role for the RAS in mediating the hypertension. Removal of the renal nerves also reduces blood pressure in SHR, suggesting that the sympathetic nervous system is important in mediating the hypertension. Because increased sympathetic activity can stimulate renin release from the kidney, it is possible that the up-regulated RAS in SHR may be due to increased sympathetic activation. In addition to the RAS and sympathetic nervous system in mediating the hypertension in SHR, treatment with antioxidants also reduces blood pressure, suggesting a role for oxidative stress in the hypertension of SHR. For example, treatment with tempol, a superoxide scavenger, reduces blood pressure...

Nongenetic Models Of Hypertension

In addition to the common genetic models of hypertension discussed earlier, there are also nongenetic models in which the hypertension is caused by infusion of a drug or by dietary manipulations or by placing a clip on the renal artery. The following is a list of such models. DOCA and salt model in aging animals This model of hypertension is a model of mineralo-corticoid hypertension developed by implanting the rats with deoxycorticosterone acetate (DOCA) pellets (typically 100 mg) and treating them with salt water (1 ). This is another model of salt-sensitive hypertension. The hypertension develops rapidly, usually within a week of the DOCA being implanted. The systems that mediate the hypertension include oxidative stress since antioxidants reduce the blood pressure (Elhaimeur et al., 2002). Agonists of serotonin receptor 5HT1A and antagonists of serotonin receptor 5HT2B reduce the blood pressure in DOCA-salt treated rats, implicating serotonin in the hypertension (Shingala and...

Transgenic Models Of Hypertension

The use of transgenic animal models to study the role that specific genes play in causing hypertension has been a focus of much research. However, to our knowledge there are no studies in which the mice were allowed to age. With the exception of a few models that are severely hypertensive and will not survive more than a few weeks or months, the lack of data in aging hypertensive trans-genics likely reflects the specific interest of the investigators who developed the strains that is, the animals were developed to answer a question not involving aging. Following we describe the most common transgenic hypertensive strains. TGR(mREN2)27. TGR(mREN2)27 is the first rat model of hypertension caused by a defined genetic defect. The TGR(mREN2)27 harbors the murine Ren-2 gene on the genetic background of the SD rat. These transgenic rats develop fulminant hypertension at an early age despite low levels of renin in plasma and kidney. High expression of the renin transgene in extrarenal tissues...

Possible Mechanisms Responsible For Hypertension

Various humoral and cardiovascular systems play a role in controlling blood pressure. Among them are the renin-angiotensin-aldosterone system, endothelin, oxida-tive stress, obesity, and the sympathetic nervous system. Aging is associated with changes in most of these systems, and this could impact the roles they may play in mediating hypertension. The following will be a concise overview of the humoral factors that could affect blood pressure in aging individuals and that are subsequently investigated in models of age-related increases in blood pressure. Superoxide is known to interact with nitric oxide (NO) to cause quenching of NO and to produce peroxy-nitrite, one of the most potent oxidative compounds known (Pryor and Squadrito, 1995). Thermodynamically speaking, the reaction of NO and superoxide is preferential since the rate of reaction is more rapid than the reaction rate of superoxide and its scavenger, superoxide dismutase (Pryor and Squadrito, 1995). The interaction between...


There are several systems for grading the fundus changes in hypertension (eg, grade I or grade II). Do not do this describe what you see. Hypertension produces a number of changes and signs in the fundus 1. Diffuse and focal or segmental constriction of the retinal arteries The older the patient, the less significant is the arterial narrowing. The earliest narrowing occurs in the retinal periphery. Tortuousity of the arteries is most evident at the disc edge, and this change is indistinguishable from arteriosclerotic changes unrelated to hypertension.

Portal hypertension

If the pressure in the portal venous system is greater than 12 mmHg then portal hypertension exists. The commonest cause of this in Western countries is alcoholic cirrhosis causing obstruction to portal venous flow, but numerous other causes are recognised and are classified (as for jaundice) into pre-hepatic, hepatic, and post-hepatic (Table 12.12). The portal venous system has been described (see Anatomy), and in portal hypertension the sites of portal-systemic communication open up, commonly resulting in oesophageal and gastric varices that can bleed profusely. The other major complication of portal hypertension is ascites. The management of variceal bleeding has been described (see Upper GI Bleeding), and includes injection sclerotherapy, endoscopic banding, TIPSS, and oesophageal transection. Rarely, splenic vein thrombosis results in left-sided portal hypertension, leading to splenomegaly and gastric varices. Splenectomy with division of the short gastric vessels is an effective...

Introduction diet and cardiovascular disease

Cardiovascular risk can be reduced by lifestyle changes, one of which is diet. There is now substantial evidence from epidemiological and clinical studies that a diet rich in fruits, vegetables, unrefined grains, fish and low-fat dairy products, and low in saturated fats and sodium, can reduce the risk of coronary heart disease and hypertension.1 People who have adopted such diets have benefited by way ofamuch lower risk of heart disease (see Table 1.1).1-4 However, such a prudent diet is not typical of what consumers in Western countries eat.3 5 It appears that consumers today are less likely to invest in long-term health if taste

Decline In Systems Redundancy With

Chronic renal failure is known to be associated with decreased number of endothelial progenitor cells (Choi et al., 2004). People with diminished numbers of nephrons in their kidneys are more likely to suffer from hypertension (Keller et al., 2003), and the number of glomeruli decreases with human age (Nyengaard and Bendtsen, 1992).

Functional foods defined

Functional foods that are marketed with claims to reduce heart disease focus primarily on the risk factors of blood cholesterol, homocysteine and hypertension. This can be done by a reduced content of food components that are known to increase risk, such as saturated fat or sodium. More recently products have been designed that are enriched in components that are thought to reduce risk. The most common 'protective' ingredients include fibres, soya, omega-3 fatty acids, phytostanols and phytosterols, and (antioxidant) vitamins. These components have cholesterol or homocysteine-lowering abilities in metabolic studies. The added ingredients may be food components that are often deficient in Western diets, such as calcium and folate. Their recommended intake could, however, be achieved by 'normal' foods. The added ingredients may also be nutrients or phytochemicals that are normally

Coronary Heart Disease

Based on their review of 43 studies that examined the relationship between physical inactivity and CHD incidence, Powell and colleagues (1987) concluded that the risk of incident CHD due to physical inactivity ranges from 1.5 to 2.4 (median 1.9). These values are similar in magnitude to other CHD risk factors, such as hypertension, hypercholesterolemia, and smoking. These data are consistent with recent evidence from the Nurses Health Study, in which physical inactivity (

Neurological Disorders

Many strokes attributed to ephedrine have actually been caused by the ingestion of ephedrine enantiomers, pseudoephedrine (82-85), phenylpropanolamine (86-93), and even methylephedrine (77). Two cases of ischemic stroke have been reported (94,95), but in neither case was their any toxicological testing to confirm the use of ephedrine. A decade-old report described the autopsy findings in three individuals with intracerebral hemorrhage and positive toxicology testing for ephedrine however, one had hypertensive cerbrovasular disease and the other had a demonstrable ruptured aneurysm (96). Intracerebral hemorrhage has also been described in suicide and attempted suicide victims who took overdoses of pseudoephedrine (97,98). There is also a report describing a patient who developed described arteritis following the intravenous administration of ephedrine during a surgical procedure (99). On the other hand, a large study to assess risk factors for stroke in young people (age 20-49) over a...

Reaching beyond Researchers

Other resources explain particular age-related diseases. The Centers for Disease Control Cardiovascular Health site contains information for lay people such as fact sheets on topics that include cholesterol, heart attacks, and high blood pressure. Of particular interest to researchers are the interactive maps that supply heart attack and stroke mortality rates for the state, gender, and racial ethnic group of choice. The site includes a list of Morbidity and Mortality Reports that relate to cardiovascular disease as well as other statistical and public-health information. NIH's Osteoporosis and Related Bone Diseases-National Resource Center offers background articles on topics of interest to researchers as well as lay people these include ''Vitamin A and Bone Health,'' ''Phytoestrogens and Bone Health,'' and ''Bone Mass Measurement What the Numbers Mean.''

General Health Benefits

2004) (3) Increases immunity Increased levels of immunoglobulin A, an essential antibody used by the immune system to protect against viral infections, were found in college students reporting having sex at least three times per week (Charnetski and Brennan, 2004) (4) Associated with reduced stress Participants who had vaginal sex in the last 2 weeks had lower blood pressure and stress response to stress-inducing tasks (Brody, 2006). Among medical residents, stress negatively affected desire, sexual arousal , and sexual satisfaction (Sangi-Haghpeykar et al, 2009) and (5) Increases physical fitness Sexual intimacy was associated with physical fitness level among Fifty Plus Fitness Association members (Bortz and Wallace, 1999) frequency of sexual activity was higher among men enrolled in an intensive physical fitness program (White etal, 1990).

Summary of strategies and implications

Techniques for phenolic phytochemical enhancement for functional food design is based on harnessing the potential of proline linked pentose-phosphate pathway (PLPPP) as the critical control point (CCP) in clonal shoots of single seed genetic origin such as herbs from the family Lamiaceae and seed sprouts in self-pollinating species such as various legumes. This strategy can be extended to develop foods with better phenolic phytochemical profile and functionality. Further it can be extended to develop functional foods and supplements with consistent ingredient profiles targeted against a disease condition. This concept is now being extended to specifically isolate antioxidants for diverse disease conditions, antimicrobials against bacterial pathogens, phytochemicals for diabetes management, angiotensin converting enzyme inhibitors for hypertension management, l-DOPA for Parkinson's management, dietary cyclooxygenase (COX-2 inhibitors) for inflammatory diseases and isoflavones for...

Characteristics of an Animal Model Modeling Pathology or Function

Animal models of human disease are seldom comprehensive. Rarely does a single system recapitulate all aspects of the human pathological process. Defining the key characteristics of a disease to be reproduced requires some knowledge of the driving force for the pathology and the symptoms. Secondary co-morbid characteristics that may be observed in the disease, but that are not critical for disease progression, would clearly be poor choices for modeling. It is not always easy to tell the difference. Before the development of molecular targets and mechanism-based approaches, pharmaceutical research and drug discovery were heavily based on animal models that reproduced symptoms seen in humans. Animals with high blood pressure or hyperglycemia were treated to determine which compounds best normalized the condition. The success of such models in predicting efficacious agents in humans depended greatly on whether the mechanisms were similar.

Project Title Betareceptors And Cardiovascular Pharmacogenomics

The focus of the candidate s research program is to determine the impact of beta-adrenergic receptor (betaAR) polymorphisms on drug response and cardiovascular disease. This broad research objective will be carried out through several studies. The first set of studies is focused in hypertension (HTN), which aim to test the hypotheses that the betaAR genes a) are associated with HTN b) are disease modifying in HTN, with a particular focus on the nocturnal blood pressure decline causing individuals to be either nocturnal dippers or nondippers and c) are important determinants of the antihypertensive response to beta-blockers. The latter aim will be tested in a small population, with focus on the blood pressure, and also through a pharmacogenetic substudy of the INVEST trial, a 22,000 patient outcomes trial in patients with hypertension and documented ischemic heart disease. The second group of studies focus on beta-blocker pharmacogenetics in heart failure. Beta-blockers...

Project Title Calcium Regulation In The Diabetic Heart

Summary Heart disease is the leading cause of death in diabetic patients, and considerable evidence is now available to support the existence of a specific diabetic cardiomyopathy that is independent of coronary artery disease and hypertension. Functional and biochemical data acquired from multicellular cardiac preparations of diabetic animals support the view that cellular mechanisms controlling cytosolic Ca2+ on a beat-to-beat basis are abnormal and contribute to impaired relaxation. The goal of this project is to characterize diabetes-induced changes in the expression and function of Ca2+ regulating proteins in isolated cardiac myocytes, and to determine the role of hyperglycemia in the pathogenesis and pathophysiology of diabetic cardiomyopathy. To test the hypothesis that abnormal Ca2+ handling occurs at the single cell level, biophysical assessment of excitation-contraction coupling will be carried out in ventricular myocytes isolated from diabetic rats. Voltage clamp techniques...

Implications for Understanding Adherence

Similarly, numerous studies have examined strategies to improve adherence. A meta-analysis by Peterson et al (2003) showed that interventions increased adherence by 4-11 , a very small amount. Kripalani and colleagues (2007) reported that just 54 of studies reviewed reported improvements in adherence while just 30 showed clinical improvements, not always related to adherence. Looking within hypertension care, Schroeder et al (2004) found that 78 of adherence studies which simplified the regimen, 44 of those using complex interventions, and 42 of those using motivational strategies reported improvements in adherence. Adherence improvements ranged from 5 to 41 . However, the heterogeneity in measurement of adherence and methods of study prevented conduct

Interventional Studies Experimental Study Designs

Once risk factors have been identified by observational studies, the impact of their reduction or elimination on health outcomes may be assessed in randomized trials, and positive results of such studies are commonly regarded as the definitive (and sometimes necessary) proof of causality of epidemiological associations. Well-known examples include reduction of cardiovascular disease endpoints by lipid lowering or antihypertensive medication in randomized trials after hyperlipidemia and hypertension had been identified as major risk factors in observational epidemiologic studies (e.g., Hebert et al., 1997 Psaty et al., 1997) or randomized clinical trials to prevent falls in elderly patients as summarized by Tinetti (2003).

Cardiovascular Disease

Despite a major decline in mortality by more than 50 in the second half of the 20th century, coronary heart disease (CHD) remains the single largest killer, accounting for 20 of all deaths in developed countries such as the United States, where mean age of manifestation of a first heart attack is 65-70 years (American Heart Association, 2005). The major risk factors for CHD, which include hypertension, hyperlipidemia, smoking and diabetes, are well established, and 80-90 of all CHD patients have prior exposure to at least one of these risk factors (Khot et al., 2003). In the United States, about 700,000 patients have a new heart attack each year. In recent years, the proportion of affected people surviving the acute stage of a heart attack has substantially increased, but the survivors have a risk of another heart attack, stroke and heart failure that is substantially higher than that of the general population (Hurst, 2002). Although there is evidence that much of the subsequent...

Dietary strategies to prevent the development of heart disease

Most investigators agree that atherosclerosis is a chronic low-grade inflammation disease.29 Pro-inflammatory factors (free radicals produced by cigarette smoking, hyperhomocysteinaemia, diabetes, peroxidised lipids, hypertension, elevated and modified blood lipids) contribute to injure the vascular endothelium, which results in alterations of its antiatherosclerotic and antithrombotic properties. This is thought to be a major step in the initiation and formation of arterial fibrostenotic lesions.29 From a clinical point of view, however, an essential distinction should be made between unstable, lipid-rich and leucocyte-rich lesions and stable, acellular fibrotic lesions poor in lipids, as the propensity of these two types of lesion to rupture into the lumen of the artery, whatever the degree of stenosis and lumen obstruction, is totally different.

Choosing the Proper Statistical Test Type Of Data

Simply to ease the interpretation of the results of an experiment. In our previous example, we showed how the mice could be categorized according to preset cut points into either lean, normal weight, or overweight classifications by their body weights. In this case, researchers may prefer the ordinal categorization in order to make statements about the relationship between some factor(s) and being normal weight or overweight rather than trying to relate the continuous measure of body weight with the factor(s). Another example is that we can categorize animals into those with hypertension and those with normal blood pressures based on their systolic blood pressure. In this case, we transform a continuous variable into a nominal one. The ease in interpretation from such analyses does come at a cost. Categorizing continuous data will strip it of some portion, perhaps a very significant portion, of the information on the relationship the researcher is investigating.

Toxicity Associated With Traditional Use by Native Populations

Density lipoprotein cholesterol, suggesting some effect on the liver. Transaminase elevations were greater in the kava-using Aboriginal community compared to those in a community where alcohol, but not kava, was consumed. This suggests that kava might be more hepatotoxic than alcohol. Shortness of breath and electrocardiograph abnormalities (tall P waves) consistent with pulmonary hypertension were seen and are interesting in that, like kava, the prescription anorexiants fenfluramine and dexfenfluramine withdrawn from the US market in 1998 were associated with pulmonary hypertension. It was also noted by the authors of this observational study that sudden death in relatively young men is more common in kava-using Aboriginal communities than in nonusing communities.

Risk Factors and Neurocognition

Various traditional biomedical risk factors for disease and newer biomarkers are associated with lower levels of cognitive function and decline. Examples include high levels of blood pressure (or hypertension Waldstein and Katzel, 2001), cholesterol (Muldoon et al, 2001), glucose (even in a non-diabetic range Taylor and MacQueen, 2007), insulin (Stolk et al, 1997), homocysteine (Elias et al, 2005), obesity (Gunstad et al, 2007), pro-inflammatory markers (e.g., interleukin-6 Yaffe et al, 2003), and indices of oxidative stress (Berr et al, 2000). Interestingly, both high and low levels of several of these risk factors (e.g. blood pressure, cholesterol, body mass index, alcohol consumption) have been related to poorer cognitive outcomes (see Waldstein et al, in press).

Chronic Diseases and Neurocognition

Medical and surgical treatments for disease affect cognitive function though in inconsistent directions. For example, prospective investigations generally indicate better cognitive outcomes for those taking antihypertensive medication than untreated hypertensives (Murray et al, 2002). Yet, results of double-blind, placebo controlled trials of antihypertensive have yielded complex and conflicting findings. Statin use may also be related to lesser prospective decline in cognitive performance (Szwast et al, 2007), although results of investigations of statin administration are mixed. Treatments for asthma (e.g., corticosteroid, theophylline) have yielded similarly mixed findings. Acute improvements in cognitive function have been associated with oxygen-related treatments for chronic obstructive pulmonary disease and obstructive sleep apnea syndrome and with hemodialysis (see Tarter et al, 2001). Coronary artery bypass surgery - a major surgical intervention - has been associated with...

Medical Decision Making

Similarly, executive functioning deserves consideration in the context of management of chronic illness and adherence to medical treatment regimens. As noted above, on average, individuals with obesity, diabetes, hypertension, peripheral vascular disease, renal dysfunction, pulmonary disease, HIV AIDS, and other illnesses demonstrate poorer executive function than individuals without these diseases. Deficits in executive function may result

Prototypes Creating Representations of Illness and Targets for Management

The CSM provides a detailed description of the processes involved in the activation of prototypes, the process that elaborates the meaning of implicit and explicit observations of somatic and functional cues. The core of the process is an ongoing scanning, checking, and comparing of somatic sensations, as well as physical and mental function, to the underlying prototype and schemata of the physical and functional self. A representation of illness is activated when the scanning or check process detects a deviation in somatic sensations and or physical and mental function that exceeds normally expected variability in the self and matches an underlying illness prototype. The representation formed at that moment is an operating hypothesis about the nature and meaning of the experienced deviations. For example, the deviations may reflect one of several acute conditions such as a migraine headache, common cold, heartburn, and or stomach ache from bad food, or a potentially chronic condition...

The mechanisms of bradycardia

The relative importance of the direct action on the myocardium and of the indirect action of the autonomic nervous system on oxygen-dependent bradycardia has been evaluated. Doubt & Evans9 confirmed the direct action of HBO on the myocardium by demonstrating a specifically oxygen-dependent bradycardia, in cats anaesthetized and curarized at a pressure of 31.3 ata (PO2 0.35 ata, PHe 31 ata). Bergo10, however, reported the disappearance of the oxygen-dependent bradycardia in rats injected with atropine at 5 ata. In fact, apart from the differences in methods and animal models, it seems possible to reconcile the outcome of both studies in differentiating two HBO effects (1) the bradycardic effect exerted on heart rate both at rest and during exercise and (2) the bradycardia occurring due to a direct effect on myocardial cells at rest, which is oxygen-dependent, appears quickly, is reversible with atropine, and is therefore probably mainly mediated by the parasympathetic system. This...

Mechanisms of the increase in arterial blood pressure

There is no consensus between authors on the existence of arterial hypertension in HBO, but all agree on the existence of an increase in peripheral vascular resistance, made obvious by calculating systemic arterial resistance21, or by the arm ankle arterial pressure ratio22. Usually the increase in resistance is related to hyperoxic vasoconstriction.

Circulatory System Diseases

The elevation of blood pressure, and diastolic pressure in particular, known as hypertension, is fairly common in middle- and late life and especially among older women. The average blood pressure for adults is 120 80, but between 110 70 and 140 90 is not considered a problem. When a person's blood pressure goes over 140 90, however, some form of treatment losing weight and keeping it off, eating less salt, cutting down on alcohol, getting more exercise, and or prescribed drugs is required. High blood pressure can be a serious problem, but it is usually viewed as potentially fatal only by virtue of its association with heart (hypertensive heart disease), kidney, (hypertensive renal disease), or cerebrovascular disease. The designation essential hypertension is used when no other signs of disease are present, or malignant hypertension when the disease has progressed rapidly. Hypertension is significantly more common among blacks than among whites, the difference between the percentage...

Project Title Cellular Responses To Stressors Of Cardiovascular Health

Been linked to cardiac arrhythmias, ischemic neuronal damage, and hypertension. We propose to examine the mechanisms of hypoxia sensing and the structure of the PAS domain containing hypoxia sensors in prokaryotes and apply this knowledge to mammalian systems. The role of recombinational DNA repair pathways in the development of heart disease will be evaluated. Heat shock proteins, which appear to play an important role in protecting against cardiac damage caused by ischemia, also will be examined. The normal adaptive response of remaining myocardium surviving infarction is myocyte hypertrophy and reactive interstitial fibrosis. We propose to determine the nature and extent of hypertrophyinduced alterations in decorin-collagen interactions and collagen fibril architecture. Elevated salt intake is one factor contributing to development of hypertension and the progression of heart disease. We propose to identify the role of brain tachykinin neurotransmitters and in the control of salt...

Use of Diuretics in the Treatment of Heart Failure in the Elderly455

Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure, while at the same time decreasing the morbidity and mortality associated with hypertension. Diuretics are currently recommended as first-line therapy for the treatment of hypertension. In addition, they remain an important component of heart failure therapy, in that they improve the symptoms of congestion, which typify the more advanced stages of heart failure. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly and reviews diuretic-related side effects that are normally encountered.

Project Title Circulatory Control During Exercise Effect Of Disease

Summary (Applicant's abstract) Exercise capacity is reduced in patients with heart disease and hypertension limiting the therapeutic value of its prescription. The long-term goal of this proposal is to understand circulatory control during exercise mediated by intramuscular somatosensory input in chronic disease. The first objective is to develop a reproducible exercise model in which cardiovascular disease is readily induced. A decerebrate rat preparation will be used and the effect of mechanically and metabolically-sensitive hindlimb afferent activity on circulatory control will be investigated. The second objective is to characterize alterations in cardiovascular control during exercise after the development of heart failure. Myocardial infarction will be induced in rats via coronary artery ligation. Changes in heart rate, blood pressure, and renal sympathetic nerve activity will be measured in response to static muscle contraction and passive muscle stretch after decerebration....

Established Coronary Disease

The incidences of other cardiovascular disease have also been linked to various aspects of hostility. For example, Williams and colleagues (2002) found that trait anger predicted stroke incidence among participants in a large national study who were aged 60 or older, and Yan and colleagues (2003) observed a link between Cook Medley scores and the development of hypertension in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Number of genetic variants contributing to genetic etiology implications for study strategy

Many late-onset diseases result from the cumulative breakdown of numerous quantitatively varying physiological systems. For example, high blood pressure can follow from abnormalities in cardiac output, blood vessel architecture, renal function, fat distribution, endothelial function and central nervous system integration, or failure of diverse homeostatic mechanisms, including baro-receptors, natriuretic peptides, renin-angiotensin-aldosterone, kinin-kallikrein, adrenergic receptors and local vasodilator mechanisms - each under varying degrees of independent genetic control.

Iop Reduction In Clinical Trials

Numerous clinical trials have demonstrated the efficacy of PG analogs in lowering IOP. Clinical trials with latanoprost,1'2'29'31'47'81 bimatoprost'1'2'44'48 and travo-prost1-3'49 have all shown that these drugs given once daily are more effective than timolol 0.5 given twice a day in reducing mean diurnal IOP in patients with ocular hypertension or glaucoma (figure 2.5). PGs have also been shown to be as effective or more effective and often better tolerated than other topical glaucoma Figure 2.5. Efficacy of PG analogs compared to timolol 0.5 twice daily in reducing IOP. (A) Latanoprost 0.005 once daily. Reprinted with permission from Camras CB. Comparison of latanoprost and timolol in patients with ocular hypertension and glaucoma a six-month masked' multicenter trial in the United States. United States Latanoprost Study Group. Ophthalmology. 1996 103 138-147. (B) Bimatoprost 0.03 once daily. Reprinted with permission from Higginbotham EJ5 Schuman EK5 Goldberg I et al. One-year...

Acute lung injury and ARDS

PAWP 18 mmHg or absence of clinical evidence of left atrial hypertension Evaluating these criteria closely, the bilateral pulmonary infiltrates on CXR are the clinical manifestation of pulmonary edema. The critical aspect of the definition is the requirement that the pulmonary capillary wedge pressure (PCWP) is less than 18 mmHg or that there is lack of clinical evidence of left atrial hypertension. These criteria eliminate heart failure as a cause of the observed edema, and thus point to an inflammatory etiology.

Positive Well Being and Physical Health

Fortunately, other studies provide stronger evidence. A good example is Kubzansky and Thurston's (2007) study of emotional vitality and coronary heart disease (CHD). A cohort of 6025 men and women aged 25-75 years who were initially free of CHD were followed for an average of 15 years, during which time 1141 developed CHD. Emotional vitality, a combination of vitality (sense of energy and pep), positive well-being (happiness and life satisfaction), and emotional self-control (feeling emotionally stable and secure), was assessed at baseline. Participants with greater emotional vitality were at markedly reduced risk for CHD, and this effect remained significant after accounting statistically for age, gender, ethnicity, marital status, educational attainment, blood pressure, cholesterol, body mass index (BMI), smoking, alcohol use, physical activity level, diabetes, hypertension, and psychological illness. All three components of emotional vitality appeared to contribute to the health...

Appraisals and Psychological Stress

As another example, the processes by which blood pressure is regulated cause increases from baseline levels in response to situational demands. If those increases occur too frequently or are too sustained, the regulatory process begins to adjust the baseline upward. Now when the stressor ends, blood pressure returns not to its preexisting resting level, but to a higher level. Over iterations of adjustment, the resting level becomes elevated, becoming hypertension (cf. Fredrikson and Matthews, 1990). A gradual shift in resting level to a value that is too extreme for the well-being of the overall system has been termed allostasis (McEwen, 2000, see Chapter 42). Consistent with this line of reasoning, chronic stress has been linked to hypertension (Sparrenberger et al, 2009).

Increased bleeding episodes

The median time to onset of an ICH event was 525 days on Tipranavir r. Many of the patients had other risk factors for intracranial hemorrhage such as CNS lesions, head trauma, recent neurosurgery, coagulaopathy, hypertension or alcohol abuse, or were receiving anticoagulant or antiplatelet agents.

Psychophysiological Pathways

Chronic occupational stress consistently predicts hypertension and atherosclerosis (Everson-Rose and Lewis, 2005 Sparrenberger et al, 2009), but social disruptions can also create chronic stress, with similar results. For example, both social isolation and crowding promote atherosclerosis in monkeys (Shively et al, 1989). Similar relationships have been found between social disruption (social isolation and lack of perceived social support) and atherosclerosis in humans (Everson-Rose and Lewis, 2005 Smith and Ruiz, 2002).

Project Title Conference On Molecular Biology Of The Heart

Summary (provided by applicant) The focus of this symposium will be on the use of molecular and genetic tools to understand cardiovascular development, function and disease. It is a very exciting time in this field and we will take advantage of the veritable explosion in information that has resulted from the genome projects of multiple organisms. Gene discovery by the time of this meeting will undoubtedly be quite advanced and we should have information about the changes in gene expression that accompany cardiovascular disease in mice and men. Another exciting hot area of investigation is the potential for stem cells in the heart. We will devote a session to the promise and practice of cardiac stem cells. The use of model organisms has made it possible to develop paradigms for early heart formation and we will use examples of these studies to explore vertebrate and invertebrate heart development. Single gene disorders have contributed a great deal of information about congenital and...

HAART lipodystrophy syndrome and cardiovascular risk

The fat redistribution and disturbances in glucose and fat metabolism resemble a clinical situation that is known as the metabolic syndrome in HIV-negative patients. This condition includes symptoms such as central adipositas, insulin resistance and hyperinsulinemia, hyperlipidemia (high LDL, Lp(a) hypertriglyceridemia and low HDL) and hypercoagulopathy. Given the well-established cardiovascular risk resulting from this metabolic syndrome, there is growing concern about a potential therapy-related increased risk of myocardial infarction in HIV patients. These fears are further sustained by reports of arterial hypertension on HAART, a high rate of smoking among HIV patients and increased levels of tissue plasmino-gen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients with lipodystrophy. Although many of the, mainly retrospective, studies dealing with this issue are inconclusive, data from a large international study (D A D study) provide evidence for an increased...

Angiotensin Convreting Enzyme

ACE may be considered the activation step in the catalytic cascade for the formation of Ang II from Ang I (Fig. 1). Although evidence of non-ACE pathways for biosynthesis of Ang II is evident (Sadjadi et al 2005a Tokuyama et al 2002), ACE likely represents the major, if not sole enzyme responsible for Ang II formation under normal physiological conditions in humans and other species. This is not to imply that ACE has no other substrates than Ang I (see below), but that a primary role for ACE is the generation of Ang II. Indeed, the identification of ACE and the characterization of the enzymatic properties must be considered a pivotal achievement in our understanding of the RAAS and cardiovascular disease, as well as leading to the successful development of ACE inhibitors in the treatment for hypertension and renal disease. ACE is a metallopeptidase composed of a single monomeric protein. Somatic ACE contains two catalytic regions designated as the amino (N) and carboxy (C) domains....

Therapeutic Influence Of Concomitant Disease

Existing disease states can influence drug therapy. Patients with decreased renal function require appropriate dose adjustments. The use of NSAIDs requires additional care and monitoring of patients with decreased renal function (72,112-115) or with compromised cardiovascular function. If patients are taking antihypertensive medications such as angiotensin-converting enzyme inhibitors and diuretics, the use of NSAIDs can interfere with their pharmacological effects (116-122). Also, patients with cardiovascular disease such as congestive heart failure requires special care for the use of NSAIDs because, in this patient population, they are most susceptible to the decreased renal perfusion effect associated with NSAIDs (123-126).

Intervention Research

Outcomes calls into question whether interventions to improve social support might benefit health. A review of 100 interventions of either group- or individual-level formats designed to modify perceptions of support availability and or skills related to seeking and receiving social support documented that a majority of interventions were successful in improving psychosocial (e.g., psychological well-being, perceptions of support availability, or receipt) and behavioral outcomes (e.g., adherence to medical treatments, maintenance of adopted health behaviors Hogan et al, 2002). However, a much smaller body of research has examined physical health impacts of social support interventions. Campbell (2003) noted that interventions for physical health conditions that involve family members, such as interventions which educate families about the target health condition and provide social support skills training, generally support the salutary benefits of family intervention for a number of...

The functional properties of vitamin D in preventing heart disease

Excessive intake of vitamin D in fortified food, over-the-counter supplements or excessive ingestion of anti-rickets pharmaceuticals can result in vitamin D poisoning. An acute toxic dose has not been established but the chronic toxic dose is more than 5O OOO IU day in adults for 1-4 months and, in children, 4OO IU day is potentially toxic. Acute toxicity effects may include muscle weakness, apathy, headache, anorexia, nausea, vomiting, and bone pain. Chronic toxicity effects include the above symptoms and constipation, anorexia, polydipsia, polyuria, backache, hyperlipidemia, and hypercalcemia. Hypercalcemia may cause permanent damage to the kidney (see http www.emedicine.com emerg topic638.htm). Arterial hypertension and aortic valvular stenosis can also result from hypervitaminosis D.

Incidence Prevalence and Risk Factors

Some common risk factors for the development of AD, including head injury, hypertension, and diabetes mellitus, are not predictors for the development of dementia in PD (136). However, the epsilon 4 isoform of the apolipoprotein E gene (APO-E4), an established risk factor for AD, has been shown to correlate with an

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.

Drugdrug Interactions

It was the observation that oral beta blockers lower IOP that stimulated development of OBBs. With the common use of oral beta blockers, there is a possibility for some patients to be prescribed both oral and topical beta blockers. Ophthalmic timolol lowered IOP to an equal extent in subjects taking oral placebo and 80 mg propranolol but had no additive effect on subjects taking 160 mg propranolol.90 Similarly, while 20 mg oral timolol administered twice daily lowered IOP, the addition of topical timolol did not further reduce IOP.91 Clinically, this finding can be important. A patient taking oral beta blockers may have little or no additional IOP effect from OBBs. With the advent of new drugs for systemic hypertension, a patient in whom an oral beta blocker is discontinued may appear to have loss of IOP control. In such patients, OBBs may restore IOP to previous levels. It is important to maintain an accurate and current history of systemic medications.

Genes predisposing to exceptional longevity

Dr Nir Barzilai and his colleagues studying Ashkenazi Jewish centenarians and their families recently found another cardiovascular pathway and gene that is differentiated between centenarians and controls (Barzilai et al., 2003). In Dr Barzilai's study, controls are the spouses of the centenarians' children. It was noted that high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particle sizes were significantly larger among the centenarians and their offspring and the particle size also differentiated between subjects with and without cardiovascular disease, hypertension and metabolic syndrome. In a candidate gene approach the researchers then searched the literature for genes that impact upon HDL and LDL particle size and the came up with hepatic lipase and cholesteryl ester transfer protein (CETP). Comparing centenarians and their offspring against controls, one variation of CETP was noted to be significantly increased among

Drugdisease Interactions

Use of OBBs is contraindicated in the presence of several cardiovascular diseases as mentioned in section 3.6.4. In a patient with uncompensated heart failure, sick sinus syndrome, or undetected bradycardia, OBBs may cause adverse symptoms or even be life-threatening. They can also lower blood pressure, potentially worsening

Regression to the mean

When measurements of a given parameter (e.g. blood pressure) are repeated, the extreme values will tend to move towards the mean value. Patients who had a high blood pressure will be found to have a lower blood pressure, whereas it will tend to increase in those who had a low blood pressure. This phenomenon has also been found within populations so that tall fathers have shorter sons and short fathers have taller sons. The practical implication of this phenomenon is that treatments must be tried on a whole range of patients. If only those patients lying at the extremes of the range are treated an apparent effect will be detected purely as a result of regression to the mean.

Interventional Therapies for Heart Failure in the Elderly485

The aging of a population replete with risk factors for heart failure (HF) (coronary heart disease, diabetes, and hypertension) coupled with a declining age-adjusted mortality rate for coronary artery and hypertensive heart diseases has created, and will continue to create, a literal explosion in the prevalence of HF in the United States. Despite advances in maximal medical therapy, however, most patients who have symptomatic HF can expect functional impairment, interludes of worsening symptomatology, and a shortened lifespan. This article updates the use of interventional therapies for the treatment of elderly patients who have HF caused by coronary artery disease, valvular heart disease, congenital heart disease, myocardial disease, and renal vascular disease.

CoQIO in heart disease

Variety of cardiovascular disorders, e.g. congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral value prolapse (Singh et al., 1998). In the apoE gene knockout mice (an excellent model of human atherosclerosis) supplementation with both vitamin E and CoQ10 was found to inhibit atherosclerosis better than with vitamin E or CoQ10 alone (Thomas et al., 2001). It is not known, however, if CoQ10 supplementation in humans can decrease atherosclerosis.

Ethical Issues in the Quality of Care

Further, while clinical practice guidelines may assist in greater consistency of care, most efforts are directed toward the cure and or treatment of medical illnesses or diseases, while minimal study is directed toward preventive efforts. The major diseases that confront the health care system today arise from social circumstances and lifestyle choices upon which present medical intervention strategies have little overall impact, at least regarding occurrence. Major chronic illnesses such as coronary artery disease, hypertension, and even some cancers are strongly correlated to lack of exercise, inadequate nutrition, smoking, and alcohol. No less challenging and resistive to medical intervention strategies are the morbidity and mortality associated with illicit drug usage, AIDS, motor-vehicle accidents, domestic violence, homelessness, homicide, suicide, and environmental toxins, known and unknown.

Nonselective Agonists

Epinephrine may cause tachycardia, extra systoles, systemic hypertension, palpitation, and anxiety. Topical use can be uncomfortable, causing tearing and stinging. Long-term use leads to allergic blepharoconjunctivitis in a significant subset of patients, which resolves when the drug is discontinued. Epinephrine is contraindi-cated in patients with narrow anterior chamber angles, because the induced my-driasis can precipitate pupillary block, inciting a pupillary-block glaucoma attack. Epinephrine is also contraindicated in aphakic patients, because topical use is associated with symptomatic, usually reversible, cystoid macular edema (CME) in roughly 13 to 30 .17,18 Of note, epinephrine-related CME has been described in aphakic, but not pseudophakic, patients. This may therefore be a problem seen only if the anterior hyaloid is disrupted following traumatic extracapsular cataract surgery. Finally, epinephrine can cause black adrenochrome deposits in the palpebral conjunctiva, on...

The Significance of Race and Ethnicity for Health

For example, for the 15 leading causes of death in the USA, blacks have higher death rates than whites for nine causes including heart disease, stroke, flu pneumonia, septicemia, homicide, cancer, diabetes, kidney diseases, and hypertension (National Center for Health Statistics, 2009). Moreover, the white-black gap in life expectancy in the USA has widened over the past 25 years due to slower improvements in black health status compared to the overall population (Mensah et al, 2005). American Indians also have markedly poorer health than whites for a number of outcomes including infant mortality, diabetes and injury related mortality, activity limitation, and self-assessed fair poor health (National Center for Health Statistics, 2009). Although the health of US Hispanic and Asian immigrants, as reflected in overall mortality rates, tends to be comparable or better than that of whites, research suggests that their health In the UK, Pakistani, Bangladeshi, and black Caribbean people...

Risk factors for coronary heart disease CHD the role of oxidative stress

Different stage in a chronic inflammatory process in the artery. The lesions of atherosclerosis represent a series of highly specific cellular and molecular responses that can be described as an inflammatory disease. Possible causes of endothelial dysfunction leading to atherosclerosis include hypercholesterol-aemia, hypertension, diabetes mellitus, cigarette smoking, elevated plasma homocysteine concentrations, infectious microrganisms and ageing. Framingham's studies have shown how each factor and combination of these factors are associated with atherosclerotic diseases.9 All these factors can be associated with oxidative stress.10-15 The beneficial effect of alpha-tocopherol and ascorbic acid is mediated by their antioxidant actions in preventing atherosclerosis. On the other hand, the effect of alpha-tocopherol could also be mediated by its antiplatelet and anti-coagulant actions, which would prevent the thrombotic consequences of atherosclerosis.16'17 Cigarette smoking,...

Test Your Ability to Analyze and Apply Your Knowledge

Some patients with hypertension (high blood pressure) are given beta-blocking drugs to lower their blood pressure. How does this effect occur 5. Why do many cold medications contain an alpha-adrenergic agonist and atropine (belladonna) Why is there a label warning for people with hypertension Why would a person with gastritis be given a prescription for atropine Explain how this drug might affect the ability to digest and absorb food.

Measuring Neighborhood Exposures

The specific features of neighborhoods that are most health relevant are likely to differ for each health outcome. For this reason, beginning with a clear conceptual framework is an important pre-requisite for delineating these features and the pathways by which they impact health. Figure 24.1 shows a conceptual framework of neighborhood environments in relation to CVD. The framework highlights features of the physical and social features of neighborhood environments and the hypothesized pathways by which they may impact CVD risk. For example, neighborhood availability and relative cost of health foods may impact diet quality which in turn may impact more proximate biological risk factors such as BMI and hypertension. Alternatively, neighborhood crime may have a direct impact on

Major Mendelian genes versus minor polygenes as predisposers

Most genetic influences on disease risks, however, occur in polygenic situations where any single contributory gene may shift the probability by no more than a few percentage points. Further, it is likely that it is the interacting set of alleles that is most relevant in determining the level of innate susceptibility of an individual to developing a disorder or disease in response to a particular environmental exposure. In recent years it has become apparent that there are multiple genetic loci which contribute to the occurrence of hypertension, a tendency to rapid weight gain, coronary heart disease, colon cancer, lung cancer and so on. This is hardly surprising. After all, the complex metabolism and physiology of the mammalian organism is, fundamentally, under genetic control, in that all proteins and other active molecules are genetically coded for, and the resultant slight interindividual variations in the molecular structure of proteins affect their biological activity.

Extent and Associations

Literate patients with hypertension and diabetes were also reported to have poorer knowledge of disease (Williams et al, 1998b). Other research studies have since confirmed this relationship in a multitude of contexts. Among individuals living with HIV AIDS, those with limited literacy were less able to define CD4 lymphocyte count and viral load and to identify antiviral medications in their regimen even with the aid of pictures (Kalichman et al, 1999 Wolf et al, 2004). A great deal of attention has also highlighted the association between low health literacy and treatment misunderstanding, including medication names, indications, and instructions. Davis and colleagues (2006a) conducted a multisite study among adults and found those with limited literacy had higher rates of misunderstanding the directions for medications provided by either the physician or the pharmacist. The problem extended to text messages and icons used for medication warnings and precautions. Finally, in perhaps...

Shift of Boundary Between Risk and Disease

For a disease that is as much feared as cancer, this is a powerful motive for the public too. However expansion of screening programs may also increase people's sense of risk or to put it the other way, undermine the illusion of health. With some screening programs identifying precursor risks (e.g. HPV infection) in a much higher proportion of the population than would ever have been likely to develop cancer, then the barriers between health and disease are blurred further. This is striking in the metabolic field where huge proportions of the population are identified with hypertension, insulin resistance, or hyperlipidemia, potentially creating an almost population-wide perception of compromised health status. The growth in personalized genetic testing - which will increasingly offer quantitative risk feedback rather than just testing for the presence or absence of highly penetrant mutations, will also add to the blurring of boundaries between health, disease risk, and disease....

Project Title Fetal Stressors Alter Longterm Myocyte Coronary Growth

Summary Babies born small at full term are 3-5 times more likely to contract ischemic heart disease than are heavy babies born to non-diabetic mothers. An index of fetal growth, like birth weight, is an independent risk factor more powerful than the well-known risk factors endorsed by the American Heart Association. However, the biological link between prenatal undergrowth and the propensity to contract coronary disease is elusive. This application is based on the hypothesis that intrauterine stressors such as hypoxia, hypertension and volume load will cause adaptive compensations of the gene expression pattern that will program the fetus for immediate survival adaptation but put the offspring at risk for adult-onset disease. During the past funding period, it was discovered that angiotensin II does not stimulate hypertrophy in vivo or in vitro, quite contrary to current dogma based on rat data. The proposal contains 3 aims designed to uncover adaptive mechanisms that are likely to...

Monogenetic Trait Variation

Although important, variation in the isoform of proteins may actually make up only a very small part of functional allelic variation. Much variation in physiology and behavior arises from a difference in expression of the gene. That is, much allelic variation may lead to more or less of a protein, rather than a different form of the protein. To illustrate the quantitative effects of allelic variation we use a modification of the example in the classical textbook on quantitative genetics by Falconer (Falconer and Mackay, 1996) and hypothesize a bi-allelic gene for systolic blood pressure (SBP) that has a decreaser allele b which causes lower blood pressure and an increaser allele B which causes higher blood pressure (see Fig. 28.2). For now, let us assume that the mean effect of all other factors translates into a SBP of 129 mm Hg and that none of these factors leads to variation between

Twin Studies on Cardiovascular Traits Often Used in Behavioral Medicine

Cardiovascular research in twin samples has suggested a clear-cut genetic contribution to hypertension (Kupper et al, 2005b McCaffery et al, 2008), diabetes (Poulsen et al, 1999), stroke (Bak et al, 2002), and coronary heart disease (Zdravkovic et al, 2002). A landmark paper was published by twin researchers of the Karolinska Institute in Sweden (Marenberg et al, 1994). They searched the National Death Registry for death certificates on 21,000 twins born in Sweden between 1886 and 1925, where both twins within a pair still lived within the country in 1961. The risk to have died from coronary heart disease when one's co-twin died before the age of 55 years was 8.1 among male monozy-gotic (MZ) twins as compared to 3.8 among male dizygotic (DZ) twins. Re-analysis using a correlated c-frailty model, which translates discrete yes no traits into a continuously distributed latent liability, yielded a heritability to die from coronary heart disease of 57 in males and 38 in females (Zdravkovic...

Gene Environment Interaction

Fortunately, if the relevant environmental factors have been measured they can be readily incorporated in the twin design. Their interaction with genetic effects can be formally tested and the relative contribution of gene-environment interaction effects to the total trait variance estimated. There are a number of ways to do this. First, the classic twin analyses can be stratified for the measured environmental factor, such that the analyses are performed in subgroups of MZ and DZ twins that are concordant for the degree of environmental exposure (Heath et al, 1998). Significantly different heritability estimates in these subgroups signal gene-environment interaction. An example for blood pressure is provided by McCaffery and colleagues (2008) who investigated Ax E gene-environment interaction in hypertension by examining the extent to which educational attainment modifies the heritability of hypertension in Vietnam-era twins. Thousands of MZ and DZ male twins provided data on their...

Benign anorectal conditions

Colonic, anorectal and peristomal varices arise as a complication of portal hypertension and can cause painless, massive lower GI hemorrhage. Nevertheless, it is the more humble anorectal conditions that present more typically with lower GI bleeding. In a review of nearly 18 000 patients with lower GI bleeding, haemorrhoids, fissure and fistula-in-ano were the cause in 11 of patients. It is, therefore, important to thoroughly examine the anorectum early in the evaluation before proceeding to more invasive and complex diagnostic methods. Digital rectal examination, proctoscopy and sigmoidoscopy should be performed in all patients with rectal bleeding. Discovery of benign anorectal disease does not eliminate the possibility of a more proximal bleeding source, and complete colonic evaluation is recommended.

Functions of the Adrenal Medulla

Produces an effect similar to continuous sympathetic nerve stimulation. The symptoms of this condition are hypertension, elevated metabolism, hyperglycemia and sugar in the urine, nervousness, digestive problems, and sweating. It does not take long for the body to become totally fatigued under these conditions, making the patient susceptible to other diseases.

Pharmacological Toxicological Effects 51 Cardiovascular Effects

A recent meta-analysis using multiple databases, from inception until November 1998, compiled all randomized, double-blind, placebo-controlled trials using monopreparations of garlic, to test the effectiveness of garlic in lowering total cholesterol (TC) (15). Inclusion criteria included trials in which participants had elevated TC, defined as 5.17 mmol L (200 mg dL) at baseline, and reported TC levels as an end point. Studies were excluded if they did not contain enough data to compute effect size. Of the 39 garlic-in-hyperlipi-demia studies identified, 21 were excluded because they were not placebo-controlled, randomized, double-blinded, did not use a monopreparation of garlic, did not report TC, or have a baseline TC meeting inclusion criteria. An additional five trials did not include enough data to perform statistical pooling. Of the 13 studies cited in the meta-analysis, 10 used Kwai powder tablets in doses of 600, 800, and 900 mg day. One study used 700 mg of spray-dried powder...

Fixed Combination Drugs

Initial therapy for glaucoma typically consists of topical medications that lower intraocular pressure (IOP), and frequently more than one agent is required to achieve adequate control of IOP. For example, initial monotherapy failed to control IOP within the first 2 years of treatment in up to 50 of glaucoma patients in the United States.1 The recent Ocular Hypertension Treatment Study randomized patients to observation or treatment in which the therapeutic goal was a relatively modest 20 IOP reduction in that study, 40 of patients randomized to treatment required more than one medication to achieve the therapeutic goal.2

Gene Stress Interaction

Gene-environment interaction can be detected by both quantitative genetic analyses and molecular studies of specific genetic variation (gene polymorphisms). Among the former, for instance, the heritability of body mass (body mass index) has been found lower among men who engage in vigorous exercise than in the less physically active (McCaffery et al, 2009), and the heritability of hypertension appears to rise with higher levels of educational attainment (McCaffery et al, 2008). Molecular studies of gene-stress interaction are more common than quantitative genetic studies, though, and these generally fall into two categories (1) those that examine how naturally occurring stressors moderate genetic influences on aspects of disease risk and, in psychiatric genetics, liability to psychopathologies of mood or conduct and (2) studies examining the genetic modulation of physiological responses to acute psychological stressors, as manipulated experimentally. The latter investigations add to a...

Modern Fixed Combinations Approved Outside The United States

The fixed combination timolol maleate 0.5 -latanoprost 0.005 (Xalacom Pfizer, Inc., New York, N.Y.) was the first beta blocker-prostaglandin combination released in 2001 after gaining regulatory approval in many regions of the world. Latanoprost was the first approved prostaglandin (in 1996) and quickly became a first-line agent of choice in the United States and around the world. Because timolol remains a popular and effective choice for adjunctive therapy, development of a fixed combination of these two agents once again reflects common clinical use. This fixed combination is approved in several countries for the reduction of IOP in patients with open-angle glaucoma and ocular hypertension. Two double-masked studies comparing timolol-travoprost fixed combination to the concomitant use of its components were conducted. In the first, 316 patients with open angle glaucoma or ocular hypertension were randomized, after a therapeutic washout, to receive either...

Clinical features

Patients with varicose veins complain of a rather nebulous set of symptoms namely leg aches, swelling, restlessness and pain or itching over specific veins. These are difficult to quantify and correlate poorly with the visible extent and size of the varicosities, which causes a problem for health care providers who are increasingly encouraged to only intervene surgically for symptoms rather than for pure cosmesis. From the epidemiological data outlined above, it would appear that female caucasian legs are more susceptible to the skin changes brought on by venous hypertension it would be reasonable to assume that they are also likely to genuinely suffer more symptoms from their varicose veins.

Project Title Impact Of Chd Risk Perception On Health Behaviors And O

Summary (Applicant's abstract) The overall goal of the proposed study is determine if perceived risk of heart disease among postmenopausal women enrolled in the Observational Study (OS) of the Women's Health Initiative (WHI) in the New York Clinical Center, differs by race, and if risk perception is related to health behaviors. The applicant's long-term career goals are to become an independent investigator with special scientific interest in determining the key psychosocial contributors to racial and gender disparity in heart disease morbidity and mortality. In the proposed study, the first phase will be to develop and pilot test a methodologically sound instrument that measures perceived risk of heart disease. The second phase will be to administer this instrument to 300 White, African-American and Hispanic women at higher risk of heart disease because of smoking status, hypertension, diabetes or high cholesterol (requiring pills) and to determine the relationship of risk perception...

Pathogenic mechanisms of ironinduced atherosclerosis

One study showed that patients with genetic haemochromatosis had significant eccentric hypertrophy of the radial artery, although none of them had arterial hypertension or evidence of cardiovascular diseases (Failla et al. 2000). The structural alteration leading to functional problems (stiffening), was largely reverted by iron depletion (Failla et al. 2000). Iron was also shown to induce early functional and structural vascular abnormalities due to endothelial dysfunction (Rooyakkers et al. 2002) which is associated with subsequent induction of oxidative stress. The radical species may also impair the mononitrogen oxide (NO) production, leading to the condition of arterial stiffness (Cheung et al. 2002). The vascular condition could be improved after administration of iron chelator (Duffy et al. 2001), which may indicate a reduced risk of cardiovascular events.

Management of pure venous ulcers

The management is primarily aimed at treating the underlying venous hypertension. Much of it can be achieved successfully in specialist nurse led clinics, on a shared care basis with community nurses, with easy access to the vascular services. There has been a recent resurgence in the popularity of perforator ligation due to the advantages of the endoscopic subfascial approach, without the difficulties relating to a large wound, by the development of endoscopic techniques through a more proximal, smaller incision ('SEPS'). In fact this technique is usually combined with open saphenous vein surgery and it is probably the latter that has the greater effect on venous hypertension.

Utility Of System 51 VSMC growth and migration

VSMCs in culture have been widely used as a model of VSMC proliferation, migration and differentiation in the artery wall 34, 49 . Analysis of the regulators of VSMC growth and migration provide insights into the role of VSMCs in the development of atherosclerosis, re-stenosis and hypertension. Most studies however, have used animal cells in culture and animal models of balloon injury and subsequent repair. Consequently, many drugs have been discovered that inhibit VSMC migration and proliferation in animal re-stenosis models, such as rat carotid artery balloon injury, but most have been unsuccessful in human trials. These studies in particular have highlighted the necessity for the generation of human tissue culture models of functional VSMC phenotypes. Human VSMC cultures are therefore of great use in preliminary drug analysis for re-stenosis research. Preliminary evaluation of a drug in monolayer culture, followed by further evaluation in a system such a human saphenous vein...

Primary hyperparathyroidism

Although it is now less common to see patients with overt symptoms or signs associated with primary hyperparathy-roidism, cases still present. The commonest clinical presentations are in patients who present with fractures, especially if through a bone cyst, or with renal calculi. Occasional patients are detected with hypercalcaemia associated with hypertension. Cardiovascular system Hypertension associated with hyperparathyroidism is irreversible once established. The post-operative drop in serum calcium can take several hours to days to stabilise. Approximately 50 of patients become hypocalcaemic post-operatively and may require calcium and even vitamin D supplementation. Full bone re-mineralisation does not occur and the hypertension and abnormal renal function, if present, do not recover.

Metabolic and Genetic Profiling

Scott and collaborators at Imperial College London have also been concerned with gene discovery using both animal and human models of the metabolic syndrome, which is the constellation of disorders related to insulin resistance and includes obesity, dyslipidaemia, diabetes mellitus, hypertension, and increased risk of atherosclerosis. A biological atlas of insulin resistance (BAIR) is currently under development using genetically engineered and environmental models of insulin resistance along with multimodality phenotyping 53 . This approach aims to integrate tran-scriptomics, phospho- and glycoproteomics, metabonomics, and structural biology to advance new hypothesis-driven research toward better understanding and treatment of metabolic syndrome.

Project Title Intermittent Hypoxia Cv Impact And Biologic Markers

Summary (provided by applicant) It is estimated that 12-20 million people in the United States have obstructive sleep apnea (OSA), a disorder typified by nightly intermittent hypoxia (IH) exposure due to upper airway obstruction during sleep. Epidemiologic, retrospective, and cross-sectional studies have identified associations between OSA and an increased risk for cardiovascular disease, e.g., stroke, ischemic heart disease, and systemic hypertension. There is emerging evidence that IH may be a more potent sympathetic nervous system stimulus than continuous hypoxia (CH), and that the pattern of hypoxia (repetitive or continuous) is a critical factor in determining physiologic response. Prior studies indicate that the episodic reoxygenation that occurs during IH represents an oxidative stress (OS) that causes cellular generation of reactive oxygen species. Additional studies suggest that OS is likely to be influential in the transcriptional activation of specific genes through which...

Cushings diseaseCushings syndrome

Clinically the patient presents with truncal obesity, moon face, hypertension, diabetes, abdominal striae, acne and a buffalo hump, and experiences profound weakness. Pituitary ACTH-producing tumours tend also to produce skin pigmentation as ACTH has a similar molecular structure to melanocyte-stimulating hormone (MSH). Because patients have a tendency to bruise easily with delicate skin which is easily damaged, and have an increased risk of infection, post-operative problems are increased.

Primary hyperaldosteronism Conns syndrome

Secondary disease is due to impaired renal perfusion most commonly associated with renal vascular disease or malignant hypertension. This results in excess production of renin from the juxta-glomerular apparatus, ultimately causing excess aldosterone production. Renin levels are therefore high. The diagnosis of Conn's syndrome rests on having a high index of suspicion. The diagnosis may not be obvious because many patients with hypertension are prescribed diuretics which cause hypokalaemia. Initially, hypertension and

The Link Between Birth Weight and Later Health

Resources, the altered metabolism and coveting of nutrients can result in a propensity for obesity. Such a scenario sometimes occurs after adoption of a young infant from an impoverished setting to an affluent country. These children are then at greater risk for becoming overweight and developing the metabolic syndrome with glucose intolerance and atherogenic dyslipidemia and are more prone to cardiovascular disease. Clinical tests indicate that these individuals also have prothrombotic and proinflammatory profiles. In addition to the human studies supporting this line of reasoning, numerous reports on rodent and sheep models have begun to delineate the hormone mechanisms and metabolic pathways accounting for these long-term effects (Murphy et al, 2006 Wintour et al, 2003). These experiments indicate that the physiological programing includes changes in the kidney, with decreases in nephron number and or size, which contribute to the later hypertension in adulthood (Moritz et al,...

The Mixed Blessing of Antenatal Corticosteroids

For some expectant women threatening to deliver early, there have been up to 10 courses administered before birthing. When treatments are repeated or prolonged, studies in rodents, sheep, and monkeys have all found adverse effects, especially on sensitive brain regions like the hippocampus (Matthews, 2000 Uno et al, 1994). When extended over many days, antenatal corti-costeroids can retard fetal growth, suppress both maternal and fetal adrenal activity, decrease thyroid activity, and affect kidney functioning in ways that would pose a long-term risk for later hypertension (Coe and Lubach, 2005 French et al, 1999 Seckl et al, 2000). One further reason for these concerns is that when administered directly to the mother before delivery, both dexamethasone and betamethasone can readily bypass the placental enzyme 116-HSD2 and then can become sequestered in fetal circulation. While examining the impact of a standard 2-day course of maternal dexamethasone in the rhesus monkey, we found...

Biological Function of Phenolic Phytochemicals

Chronic and infectious diseases have become the primary cause of mortality and are expected to become a major public health challenge. These chronic diseases such as cardiovascular disease, hypertension, diabetes mellitus, and some forms of cancer, have now been associated with changes in diet and lifestyle associated with calorie sufficiency. These include excessive dietary carbohydrate and fat intake, low intake of fruits and vegetables, smoking, lack of physical activity, and exposure to environmental toxins (92). Another well described function of phenolic phytochemicals is the prevention of cardiovascular diseases (CVDs). The lower incidences of CVDs in populations consuming wine as part of their regular diet is well established, and is often referred to as the French paradox (103). Recent research into the beneficial effects of wine has led to an understanding that resveratrol, which is a phenolic phytochemical, is the active component in wine responsible for its beneficial...

Project Title Jackson Heart Studycoordinating Center

Summary Despite encouraging declines over the past three decades, cardiovascular disease (CVD) remains the number one cause of death in the U.S. A number of risk factors for coronary heart disease (CHD) and stroke have been identified however, relatively few population-based studies have examined CVD in a large group of African-Americans. Existing evidence indicated that death rates in Mississippi are the highest in the nation and particularly high among African-Americans. Between 1980 and 1995, the decline in CVD death rates has been the slowest among African-American men and women in Mississippi relative to other groups in the state and nation. The Jackson Heart Study (JHS) is a single-site prospective epidemiologic investigation of CVD among approximately 6,500 African-Americans ages 35 to 84, from Jackson, Mississippi metropolitan area. The primary objective of the JHS is to investigate the causes of CVD in African- Americans to learn how to best prevent this group of diseases in...

Chronic Negative Affect

Deficits in socioemotional skills may ultimately stabilize into enduring risks for emotional disorders, such as anxiety, depression, and other chronic negative emotional states. These states may act as predisposing factors for adverse physical health outcomes (Hemingway et al, 2003). For example, hostility has been tied to the development of metabolic syndrome among children and adolescents (Dembroski et al, 1985) and to an increased risk for coronary heart disease (CHD) and hypertension (Julkunen et al, 1994). Major depression, depressive symptoms, and history of depression have all been identified as predictors of cardiac events (Frasure-Smith et al, 1995), and depression is a risk factor for mortality following myocardial infarction, independent of cardiac disease severity (Frasure-Smith et al, 1995). State depression, as well as clinical depression, have been related to sustained suppressed immunity (Herbert and Cohen, 1993). Anger appears to play a significant role in the...

Impact of Early Environment on Biological Stress Responses

Chronic or recurrent activation, they can be associated with deleterious long-term implications for health (e.g., Seeman and McEwen, 1996 Uchino et al, 1996, see Chapter 42). For example, excessive or repeated discharge of epinephrine or norepinephrine can lead to the suppression of cellular immune function, produce hemodynamic changes such as increases in blood pressure and heart rate, provoke abnormal heart rhythms such as ventricular arrhythmias, and produce neurochemical imbalances that may relate to psychiatric disorders. Intense, rapid, and or long-lasting sympathetic responses to repeated stress or challenge have been implicated in the development of hypertension and coronary artery disease (McEwen and Stellar, 1993).

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