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Hypertension

Hypertension, commonly referred to as "high blood pressure", is a medical condition where the blood pressure is chronically elevated. While it is formally called arterial hypertension, the word "hypertension" without a qualifier usually refers to arterial hypertension. Hypertension gives a higher risk of heart attack or stroke than any other disease. Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure.

Hypertension can be classified as either essential or secondary. Essential hypertension is the term used when no specific medical cause can be found to explain a patient's condition. Secondary hypertension means that the high blood pressure is a result of (i.e. secondary to) another condition, such as kidney disease or certain tumors.

Recently, the JNC 7 (the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) has defined blood pressure 120/80 mmHg to 139/89 mmHg as "prehypertension." Prehypertension is not a disease category; rather, it is a designation chosen to identify individuals at high risk of developing hypertension.

The Mayo Clinic website indicates that your blood pressure is "normal if it's below 120/80" but that "some data indicate that 115/75 mm Hg should be the gold standard."

"In patients with diabetes mellitus or kidney disease studies have shown that blood pressure over 130/80 mmHg should be considered a risk factor and warrants treatment. Even lower numbers are considered diagnostic using home blood pressure monitoring devices.

Current Research

For current research articles click - here

Etiology of Essential Hypertension

Environment

A number of environmental factors have been implicated in the development of hypertension, including salt intake, obesity, occupation, alcohol intake, family size, stimulant intake, excessive noise exposure, and crowding.

Salt Sensitivity

Sodium is the environmental factor that has received the greatest attention. It is to be noted that approximately 60% of the essential hypertension population is responsive to sodium intake.

Role of Renin

Renin is an enzyme secreted by the juxtaglomerular cells of the kidney and linked with aldosterone in a negative feedback loop.The range of plasma renin activities observed in hypertensive subjects is broader than in normotensive individuals. In consequence, some hypertensive patients have been defined as having low-renin and others as having high-renin essential hypertension.

Insulin Resistance

Insulin is a polypeptide hormone secreted by the pancreas. Its main purpose is to regulate the levels of glucose in the body, it also has some other effects. Insulin resistance and/or hyperinsulinemia have been suggested as being responsible for the increased arterial pressure in some patients with hypertension. This feature is now widely recognized as part of syndrome X, or the metabolic syndrome.

Sleep Apnea

Sleep apnea is a common, under recognized cause of hypertension. It is best treated with weight loss, nocturnal nasal positive airway pressure, or the Mandibular advancement splint (MAS).

Genetics

Hypertension is one of the most common complex genetic disorders, with genetic heritability averaging 30%. Data supporting this view emerge from animal studies as well as in population studies in humans. Most of these studies support the concept that the inheritance is probably multifactorial or that a number of different genetic defects each have an elevated blood pressure as one of their phenotypic expressions.

More than 50 genes have been examined in association studies with hypertension, and the number is constantly growing.

Other Etiologies

There are some anecdotal or transient causes of high blood pressure. These are not to be confused with the disease called hypertension in which there is an intrinsic physiopathological mechanism as described above.

Etiology of Secondary Hypertension

Only in a small minority of patients with elevated arterial pressure can a specific cause be identified. These individuals will probably have an endocrine or renal defect that if corrected would bring blood pressure back to normal values.

Renal Hypertension:

Hypertension produced by diseases of the kidney. A simple explanation for renal vascular hypertension is that decreased perfusion of renal tissue due to stenosis of a main or branch renal artery activates the renin-angiotensin system.

Adrenal Hypertension:

Hypertension is a feature of a variety of adrenal cortical abnormalities. In primary aldosteronism there is a clear relationship between the aldosterone-induced sodium retention and the hypertension. In patients with pheochromocytoma increased secretion of catecholamines such as epinephrine and norepinephrine by a tumor (most often located in the adrenal medulla) causes excessive stimulation of [adrenergic receptors], which results in peripheral vasoconstriction and cardiac stimulation. This diagnosis is confirmed by demonstrating increased urinary excretion of epinephrine and norepinephrine and/or their metabolites (vanillylmandelic acid).

Hypercalcemia

Coarctation of the Aorta

Diet:

Certain medications, especially NSAIDS (Motrin/ibuprofen) and steroids can cause hypertension. Ingestion of imported licorice (Glycyrrhiza glabra) can cause secondary hypoaldosteronism, which itself is a cause of hypertension.

Age:

Over time, the number of collagen fibers in artery and arteriole walls increases, making blood vessels stiffer. With the reduced elasticity comes a smaller cross-sectional area in systole, and so a raised mean arterial blood pressure.



Pathophysiology

Most of the secondary mechanisms associated with hypertension are generally fully understood, and are outlined at secondary hypertension. However, those associated with essential (primary) hypertension are far less understood. What is known is that cardiac output is raised early in the disease course, with total peripheral resistance (TPR) normal; over time cardiac output drops to normal levels but TPR is increased. Three theories have been proposed to explain this:
  • Inability of the kidneys to excrete sodium, resulting in natriuretic factors such as Atrial Natriuretic Factor being secreted to promote salt excretion with the side-effect of raising total peripheral resistance.
  • An overactive renin / angiotension system leads to vasoconstriction and retention of sodium and water. The increase in blood volume leads to hypertension.
  • An overactive sympathetic nervous system, leading to increased stress responses.
It is also known that hypertension is highly heritable and polygenic (caused by more than one gene) and a few candidate genes have been postulated in the etiology of this condition.

Signs and Symptoms

Hypertension is usually found incidentally - "case finding" - by healthcare professionals. It normally produces no symptoms.

Malignant hypertension (or accelerated hypertension) is distinct as a late phase in the condition, and may present with headaches, blurred vision and end-organ damage.

It is recognised that stressful situations can increase the blood pressure.

Hypertension is often confused with mental tension, stress and anxiety. While chronic anxiety is associated with poor outcomes in people with hypertension, it alone does not cause it.

Hypertensive Urgencies and Emergencies

Hypertension is rarely severe enough to cause symptoms. These typically only surface with a systolic blood pressure over 240 mmHg and/or a diastolic blood pressure over 120 mmHg. These pressures without signs of end-organ damage (such as renal failure) are termed "accelerated" hypertension. When end-organ damage is possible or already ongoing, but in absence of raised intracranial pressure, it is called hypertensive emergency. Hypertension under this circumstance needs to be controlled, but prolonged hospitalization is not necessarily required. When hypertension causes increased intracranial pressure, it is called malignant hypertension. Increased intracranial pressure causes papilledema, which is visible on ophthalmoscopic examination of the retina.

Complications

While elevated blood pressure alone is not an illness, it often requires treatment due to its short- and long-term effects on many organs. The risk is increased for:
  • Cerebrovascular accident (CVAs or strokes)
  • Myocardial infarction (heart attack)
  • Hypertensive cardiomyopathy (heart failure due to chronically high blood pressure)
  • Hypertensive retinopathy - damage to the retina
  • Hypertensive nephropathy - chronic renal failure due to chronically high blood pressure

Pregnancy

Although few women of childbearing age have high blood pressure, up to 10% develop hypertension of pregnancy. While generally benign, it may herald three complications of pregnancy: pre-eclampsia, HELLP syndrome and eclampsia. Follow-up and control with medication is therefore often necessary.

Diagnosis

Hypertension is usually abbreviated as HTN.

Measuring Blood Pressure

Diagnosis of hypertension is generally on the basis of a persistently high blood pressure. Usually this requires three separate measurements at least one week apart. Exceptionally, if the elevation is extreme, or end-organ damage is present then the diagnosis may be applied and treatment commenced immediately.

Obtaining reliable blood pressure measurements relies on following several rules and understanding the many factors that influence blood pressure reading.

For instance, measurements in control of hypertension should be at least 1 hour after caffeine, 30 minutes after smoking and without any stress. Cuff size is also important. The bladder should encircle and cover two-thirds of the length of the arm. The patient should be sitting for a minimum of five minutes. The patient should not be on any adrenergic stimulants, such as those found in many cold medications.

When taking manual measurements, the person taking the measurement should be careful to inflate the cuff suitably above anticipated systolic pressure. The person should inflate the cuff to 300 mmHg and then slowly release the air while palpating the radial pulse. After one minute, the cuff should be reinflated to 30 mmHg higher than the pressure at which the radial pulse was no longer palpable. A stethoscope should be placed lightly over the brachial artery. The cuff should be at the level of the heart and the cuff should be deflated at a rate of 2 to 3 mmHg/s. Systolic pressure is the pressure reading at the onset of the sounds described by Korotkoff (Phase one). Diastolic pressure is then recorded as the pressure at which the sounds disappear (K5) or sometimes the K4 point, where the sound is abruptly muffled. Two measurements should be made at least 5 minutes apart, and, if there is a discrepancy of more than 5 mmHg, a third reading should be done. The readings should then be averaged. An initial measurement should include both arms. In elderly patients who particularly when treated may show orthostatic hypotension, measuring lying sitting and standing BP may be useful. The BP should at some time have been measured in each arm, and the higher pressure arm preferred for subsequent measurements.

BP varies with time of day, as may the effectiveness of treatment, and archetypes used to record the data should include the time taken. Analysis of this is rare at present.

Automated machines are commonly used and reduce the variability in manually collected readings. Routine measurements done in medical offices of patients with known hypertension may incorrectly diagnose 20% of patients with uncontrolled hypertension.

Distinguishing Primary vs. Secondary Hypertension

Once the diagnosis of hypertension has been made it is important to attempt to exclude or identify reversible (secondary) causes:
  • Distinguishing primary vs. secondary hypertension
  • Once the diagnosis of hypertension has been made it is important to attempt to exclude or identify reversible (secondary) causes

Investigations Commonly Performed in Newly Diagnosed Hypertension

Tests are undertaken to identify possible causes of secondary hypertension, and seek evidence for end-organ damage to the heart itself or the eyes (retina) and kidneys. Diabetes and high cholesterol levels being additional risk factors for the development of cardiovascular disease are also tested for as they will also require management.

Blood tests commonly performed include:
  • Creatinine (renal function) - to identify both underlying renal disease as a cause of hypertension and conversely hypertension causing onset of kidney damage. Also a baseline for later monitoring the possible side-effects of certain antihypertensive drugs.
  • Electrolytes (sodium, potassium)
  • Glucose - to identify diabetes mellitus
  • Cholesterol
Additional tests often include:
  • Testing of urine samples for proteinuria - again to pick up underlying kidney disease or evidence of hypertensive renal damage.
  • Electrocardiogram (EKG/ECG) - for evidence of the heart being under strain from working against a high blood pressure. Also may show resulting thickening of the heart muscle (left ventricular hypertrophy) or of the occurrence of previous silent cardiac disease (either subtle electrical conduction disruption or even a myocardial infarction).
  • Chest X-ray - again for signs of cardiac enlargement or evidence of cardiac failure.


Epidemiology

The level of blood pressure regarded as deleterious has been revised down during years of epidemiological studies. A widely quoted and important series of such studies is the Framingham Heart Study carried out in an American town: Framingham, Massachusetts. The results from Framingham and of similar work in Busselton, Western Australia have been widely applied. To the extent that people are similar this seems reasonable, but there are known to be genetic variations in the most effective drugs for particular sub-populations. Recently (2004), the Framingham figures have been found to overestimate risks for the UK population considerably. The reasons are unclear. Nevertheless the Framingham work has been an important element of UK health policy.

Treatment

Lifestyle Modification

Doctors recommend weight loss and regular exercise as the first steps in treating mild to moderate hypertension. These steps are highly effective in reducing blood pressure, although most patients with moderate or severe hypertension end up requiring indefinite drug therapy to bring their blood pressure down to a safe level. Discontinuing smoking does not directly reduce blood pressure, but is very important for people with hypertension because it reduces the risk of many dangerous outcomes of hypertension, such as stroke and heart attack. An increase in daily calcium intake has also been shown to be highly effective in reducing blood pressure.

Mild hypertension is usually treated by diet, exercise and improved physical fitness. A diet rich in fruits and vegetables and low fat or fat-free dairy foods and moderate or low in sodium lowers blood pressure in people with hypertension. This diet is known as the DASH diet (Dietary Approaches to Stop Hypertension), and is based on National Institutes of Health sponsored research. Dietary sodium (salt) may worsen hypertension in some people and reducing salt intake decreases blood pressure in a third of people. Many people choose to use a salt substitute to reduce their salt intake. Regular mild exercise improves blood flow, and helps to lower blood pressure. In addition, fruits, vegetables, and nuts have the added benefit of increasing dietary potassium, which offsets the effect of sodium and acts on the kidney to decrease blood pressure.

Reduction of environmental stressors such as high sound levels and over-illumination can be an additional method of ameliorating hypertension. Biofeedback is also used particularly device guided paced breathing.

Impact of Race

In a summary of recent research Jules P. Harrell, Sadiki Hall, and James Taliaferro describe how a growing body of research has explored the impact of encounters with racism or discrimination on physiological activity. "Several of the studies suggest that higher blood pressure levels are associated with the tendency not to recall or report occurrences identified as racist and discriminatory." In other words, failing to recognize instances of racism has a direct impact on the blood pressure of the person experiencing the racist event. Investigators have reported that physiological arousal is associated with laboratory analogues of ethnic discrimination and mistreatment.

The interaction between high blood pressure and racism has also been documented in studies by Claude Steele, Joshua Aronson, and Steven Spencer on what they term "stereotype threat."

Medications

There are many classes of medications for treating hypertension, together called antihypertensives, which — by varying means — act by lowering blood pressure. Evidence suggests that reduction of the blood pressure by 5-6 mmHg can decrease the risk of stroke by 40%, of coronary heart disease by 15-20%, and reduces the likelihood of dementia, heart failure, and mortality from vascular disease.

The aim of treatment should be blood pressure control to <140/90 mmHg for most patients, and lower in certain contexts such as diabetes or kidney disease (some medical professionals recommend keeping levels below 120/80 mmHg). Each added drug may reduce the systolic blood pressure by 5-10 mmHg, so often multiple drugs are necessary to achieve blood pressure control.

Commonly used drugs include:
  • ACE inhibitors such as captopril, enalapril, fosinopril (Monopril®), lisinopril (Zestril®), quinapril, ramipril (Altace®)
  • Angiotensin II receptor antagonists: eg, irbesartan (Avapro®), losartan (Cozaar®), valsartan (Diovan®), candesartan (Atacand®)
  • Alpha blockers such as doxazosin, prazosin, or terazosin
  • Beta blockers such as atenolol, labetalol, metoprolol (Lopressor®, Toprol-XL®), propranolol.
  • Calcium channel blockers such as amlodipine (Norvasc®), diltiazem, verapamil
  • Diuretics: eg, bendroflumethiazide, chlortalidone, hydrochlorothiazide (also called HCTZ)
  • Combination products (which usually contain HCTZ and one other drug)
Which type of many medications should be used initially for hypertension has been the subject of several large studies and various national guidlelines.

The ALLHAT study showed a slightly better outcome and cost-effectiveness for the thiazide diuretic chlortalidone compared to anti-hypertensives. Whilst a subsequent smaller study (ANBP2) did not show this small difference in outcome and actually showed a slightly better outcome for ACE-inhibitors in older male patients.

Whilst thiazides are cheap, effective, and recommended as the best first-line drug for hypertension by many experts, they are not prescribed as often as some newer drugs. Arguably, this is because they are off-patent and thus rarely promoted by the drug industry. Although physicians may start with non-thiazide antihypertensive medications if there is a compelling reason to do so. An example is the use of ACE-inhibitors in diabetic patients who have evidence of kidney disease, as they have been shown to both reduce blood pressure and slow the progression of diabetic nephropathy. In patients with coronary artery disease or a history of a heart attack, beta blockers and ACE-inhibitors both lower blood pressure and protect heart muscle over a lifetime, leading to reduced mortality.

Advice in the United Kingdom

The risk of beta-blockers provoking type 2 diabetes led to their downgrading to fourth-line therapy in the United Kingdom in June 2006, in the revised national guidelines.

Advice in the United States

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) in the United States recommends starting with a thiazide diuretic if single therapy is being initiated and another medication is not indicated.


(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Hypertension)





Findings From Current Research

Microlevel Determinants of Blood Pressure Among Women of Two Ethnic Groups in a Periurban Area of Kolkata City, India.

Authors: Ghosh R.

Epidemiology and Health Services Evaluation Department, S. Daniel Abraham International Center for Health and Nutrition, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Blood pressure (BP) trends vary cross-culturally, and studies on the risk factors associated with hypertension are limited in periurban regions of India. This study was conducted to examine the effect of socioeconomic factors (income, expenditure, activity time) and anthropometric measurements (skinfolds of biceps, triceps, subscapular, supra iliac, and body mass index) on 102 Munda (tribe) and 135 Pod (caste) women of childbearing age in a periurban area of Kolkata city. Results indicate that Munda women had significantly higher diastolic BP in the 30+ age group. However, no difference in the systolic and diastolic BP was observed between the two groups, when the socioanthropometric factors were controlled as covariates. Also, according to the JNC (JNC, 2004, The JNC 7 Report NIH Publication No. 04-5230) classification of hypertension, no significant difference in hypertension was noted between the women of the two social groups. But the risk factors associated with hypertension varied between the two ethnic groups. Expenditure on alcohol and activity time was associated with hypertension among the Munda, while body mass index was significantly associated with hypertension among the Pod women. Alcohol consumption is a rare phenomenon among Indian women. Yet, Munda women in this transitional periurban environment, in spite of high poverty were more inclined to spent their earnings in alcohol consumption (due to their cultural preferences), increasing the risk of hypertension in their childbearing age. Am. J. Hum. Biol. 19:409-415, 2007. (c) 2007 Wiley-Liss, Inc.

Journal: Am J Hum Biol. 2007 Apr 9;19(3):409-415
Adapted from PubMed; click here to access full journal article.




Treatment Options for Prehypertension.

Authors: Nesbitt SD.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

PURPOSE OF REVIEW: Prehypertension is a recognized stage of blood pressure but treatment standards have not yet been established. This review will focus on the treatment considerations in prehypertension. RECENT FINDINGS: Previous approaches to prehypertensive blood pressure have focused on the role of nonpharmacologic modalities alone. The recently published Trial of Preventing Hypertension (TROPHY) is the first study of pharmacologic intervention in this category of blood pressure. SUMMARY: TROPHY forged new territory in the area of pharmacologic treatment for prehypertension. The safety and tolerability of the angiotensin receptor blocker treatment in the trial offer a new option to clinicians attempting to avoid the ravages of hypertension in the patients they treat. Furthermore the stage is properly set for additional research in treatments for prehypertension.

Journal: Curr Opin Nephrol Hypertens. 2007 May;16(3):250-5.
Adapted from PubMed; click here to access full journal article.




Predictors of Outcome in Chronic Thromboembolic Pulmonary Hypertension.

Authors: Bonderman D, Skoro-Sajer N, Jakowitsch J, Adlbrecht C, Dunkler D, Taghavi S, Klepetko W, Kneussl M, Lang IM.

Departments of Cardiology, Core Unit for Medical Statistics and Informatics, and Cardiothoracic Surgery, Medical University of Vienna, and the Department of Pulmonology, Wilhelminenspital, Vienna, Austria.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intraluminal thrombus organization and fibrous obliteration of pulmonary arteries. Recently, associated medical conditions such as splenectomy, ventriculoatrial shunt for the treatment of hydrocephalus, permanent central intravenous lines, inflammatory bowel disease, and osteomyelitis were found to be associated with the development of CTEPH. The study aim was to define the impact of these novel risk factors on survival. METHODS AND RESULTS: Between January 1992 and December 2006, 181 patients diagnosed with CTEPH were tracked with the use of our center's customized computer database. A Cox regression model was used to examine relations between survival and associated medical conditions, age, sex, hemodynamic parameters, modified New York Heart Association functional class at diagnosis, CTEPH type, pulmonary endarterectomy, and anti-cardiolipin antibodies/lupus anticoagulant. During a median observation time of 22.1 (range, 0.03 to 152) months, the clinical end point of cardiovascular death or lung transplantation occurred in 48 cases (27%). Pulmonary endarterectomy (hazard ratio, 0.14; 95% CI, 0.05 to 0.41; P=0.0003), associated medical conditions (hazard ratio, 3.17; 95% CI, 1.70 to 5.92; P=0.0003), and pulmonary vascular resistance (hazard ratio, 1.02; 95% CI, 1.00 to 1.04; P=0.04) were predictors of survival. Thirty-day postoperative mortality (24% versus 9%) and the incidence of postoperative pulmonary hypertension (92% versus 20%) were substantially higher in patients with associated medical conditions. CONCLUSIONS: CTEPH-predisposing medical conditions, such as splenectomy, permanent central intravenous lines, and certain inflammatory disorders, predict poor survival in CTEPH.

Journal: Circulation. 2007 Apr 9;
Adapted from PubMed; click here to access full journal article.




Blood Pressure and Hypertension in an American Colony (Puerto Rico) and on the USA Mainland Compared, 1886-1930.

Authors: Godoy R, Goodman E, Gravlee C, Levins R, Seyfried C, Caram M, Jha N.

Heller School, Brandeis University, Waltham, MA 02454-9110, USA.

We compare blood pressure and hypertension between adult men on the USA mainland and in Puerto Rico born during 1886-1930 to test hypotheses about the link between cardiovascular health and large socioeconomic and political changes in society: (a) 8853 men surveyed in Puerto Rico in 1965 and (b) 1449 non-Hispanic White men surveyed on the mainland during 1971-1975. Systolic and diastolic blood pressure and hypertension were regressed separately on demographic and socioeconomic variables and cardiovascular risk factors. Mainland men not taking anti-hypertensive medication showed statistically significant improvements in systolic blood pressure and hypertension at the beginning of the century and men in Puerto Rico showed improvements in diastolic blood pressure but only during the last two quinquenniums. An average man born on the mainland during the last birth quinquennium (1926-1930) had 7.4-8.7mmHg lower systolic blood pressure and was 61% less likely to have systolic hypertension than one born before 1901. On average Puerto Rican men born during 1921-1925 had approximately 1.7mmHg lower diastolic blood pressure than men born before 1901. Analyses of secular trends in cardiovascular health complements analyses of secular trends in anthropometric indicators and together provide a fuller view of the changing health status of a population.

Journal: Econ Hum Biol. 2007 Mar 15;
Adapted from PubMed; click here to access full journal article.




Relationships Between the "Eating Inventory" Factors, Socioeconomic Status, Anthropometric Body Adiposity Indexes and Health Risks in Czech Population

Authors: Wagenknecht M, Hainer V, Kunesova M, Bellisle F, Parizkova J, Braunerova R, Hill M, Lajka J.

Endokrinologicky ustav, Praha. mwagenknecht@endo.cz

BACKGROUND: The aim of the study was to compare and evaluate psychological traits of eating behavior assessed using the Eating Inventory (El) known also as the Three Factor Eating Questionnaire (TFEQ) and their relationship to body adiposity, health and social characteristic in a quota sample of Czech adults. METHODS AND RESULTS: The sample included 1624 women and 1429 men who were interviewed individually by instructed investigators. The sample was quota representative--for gender, age, size of residential location, region and socioeconomic status in Czech adults. Anthropometric data were obtained together with socioeconomic and lifestyle information. Subjects filled out the EI. Health status was evaluated according to the data reported by GPs. Our results show, that women had higher restraint but lower disinhibition and hunger scores than men. Hunger and disinhibition were always strongly associated, whereas restraint was negatively related to the other two factors in men, and to hunger in women. In both men and women an educational level positively correlated with dietary restraint and negatively with hunger. However, significant negative relationship between educational level and disinhibition was revealed only in men. In backward stepwise regression analysis both dietary restraint and disinhibition predicted BMI and waist circumference. BMI and waist circumference were negatively related to restraint, but positively to disinhibition. Restraint and disinhibition were associated with prevalence of comorbidities in men, while disinhibition and hunger were in women. Individuals with high scoring in disinhibition score (upper quartile) exhibited significantly higher prevalence of hypertension, cardiovascular diseases and hyperlipidaemia than those who scored low (lower quartile). These relationships were most marked in middle-aged subjects. CONCLUSIONS: Psychological traits of eating behaviour seem to have an important role in the development and clinical expression of body adiposity. Especially disinhibition is significantly associated with BMI and waist circumference and prevalence of several pathologies.

Journal: Cas Lek Cesk. 2007;146(3):284-6, 287-91.
Adapted from PubMed; click here to access full journal article.




Treating Hypertension in the Patient with Overt Diabetic Nephropathy.

Authors: Lewis EJ.

Department of Medicine, Rush University Medical Center, Chicago, IL.

Arterial blood pressure is a major determinant of renal and cardiovascular outcomes in diabetic nephropathy. There is a proportional relationship between the systolic blood pressure and renal and mortality outcomes. Decreasing the diastolic pressure does not significantly decrease these outcomes. Irrespective of the magnitude of pretreatment systolic hypertension in the patient with type 2 diabetic nephropathy, the systolic pressure achieved with antihypertensive therapy is the important determinant of renal and cardiovascular risk. Achieving a lower systolic pressure down to 120 mm Hg is associated with substantial risk reduction. Although the data are limited, systolic blood pressure less than 120 mm Hg may be associated with increased all-cause mortality in this patient population, increasing the possibility of a J-curve response. A marked decrease in diastolic pressure, which is a danger when undertaking aggressive therapy with the goal of decreasing the systolic pressure to 130 mm Hg, can be associated with an increased risk of cardiac events. The renoprotective and proteinuria-decreasing effects of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers recommend these agents as the standard of care in type 2 diabetic nephropathy. In addition to angiotensin-converting enzyme inhibitor and angiotensin-receptor blocker therapy, controlling the systolic blood pressure in this difficult to control patient population may require the use of 3 or more antihypertensive agents.

Journal: Semin Nephrol. 2007 Mar;27(2):182-94.
Adapted from PubMed; click here to access full journal article.




Pulmonary Hypertension: A Disease of Tethers, SNAREs and SNAPs?

Authors: Sehgal PB, Mukhopadhyay S.

Cell Biology & Anatomy, New York Medical College, Valhalla, New York, United States; Medicine, New York Medical College, Valhalla, New York, United States.

Histological and electron microscopic studies over the last four decades have highlighted plump, enlarged endothelial, smooth muscle and fibroblastic cellular elements with increased endoplasmic reticulum (ER), Golgi stacks and vacuolation in pulmonary arterial lesions in human and in experimental [hypoxia and monocrotaline(MCT)] pulmonary arterial hypertension (PAH). However, the contribution of disrupted intracellular membrane trafficking in the pathobiology of this disease has received insufficient attention. Recent studies suggest a pathogenetic role of the disruption of intracellular trafficking of vasorelevant proteins and cell-surface receptors in the development of this disease. The purpose of this essay is to highlight the molecular regulation of vesicular trafficking by membrane tethers, SNAREs and SNAPs and to suggest how their dysfunction, directly and/or indirectly, might contribute to development of PAH in experimental models and in man, including that due to mutations in BMPR2. Key words: intracellular vesicular trafficking, Golgi blockade, N-ethylmaleimide sensitive factor (NSF), tethers, SNAREs and SNAPs, NO and eNOS.

Journal: Am J Physiol Heart Circ Physiol. 2007 Apr 6;
Adapted from PubMed; click here to access full journal article.




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