Mummies and Heart Disease

Now this article got my attention. Don't blame everything to the fast foods...

November 23, 2009 (Orlando, Florida) — Checking in on some very old patients with cutting-edge computed tomographic (CT) technology reveals that atherosclerosis might not necessarily be a disease caused by a modern lifestyle. Imaging scans of Egyptian mummies, including some 3500 years old, reveals evidence of atherosclerosis, report researchers.

"There were parts of the cardiovascular system [amazingly] intact," said researcher Dr Randall Thompson (University of Missouri-Kansas City School of Medicine). "We found that on CT scan, atherosclerosis, the disease that we deal so much with, looks surprisingly like it does in our modern-day patients."

Presenting their findings here at the American Heart Association 2009 Scientific Sessions last week, Thompson, along with coinvestigator Dr Sam Wann (Wisconsin Heart Hospital, Milwaukee), said the mummies included in the study all had high social status and many served in the court of the Pharaoh or as priests or priestesses. He added that the group had not expected to see any signs of cardiovascular disease because atherosclerosis is traditionally thought of as a disease caused by an unhealthy fast-food diet, smoking, and lack of exercise. This study, however, suggests the need to look beyond traditional risk factors.

"It looks like people 3000 years ago had the propensity, at least under the circumstances of living in the King's court, to develop this disease," said Wann.

The Mummy and the Skeptical Cardiologist

During a media briefing at the AHA last week, researchers said that the study began when Dr Gregory Thomas (University of California, Irvine), another member of the team, was touring the Museum of Egyptian Antiquities in Cairo last year and came upon Pharaoh Merenptah (c. 1213-1203 BCE). Information on the Pharaoh's nameplate stated that he died at approximately age 60 and was afflicted with atherosclerosis. Skeptical that someone who lived so long ago would have atherosclerosis, American and Egyptian researchers initiated the study to determine if the diagnosis was correct and, if it was, to determine how common atherosclerosis was in a small sample of ancient Egyptians.

Working with Dr Adel Allam (Al Azhar Medical School, Cairo, Egypt) and Dr Michael Miyamoto (University of California, San Diego), as well as with archeologists and mummy experts, in February 2009, the researchers scanned 22 mummies, the oldest of which was 3500 years old. The coronary, aortic, and peripheral vasculature was identified in 16 of the specimens. Definite or probable atherosclerosis was present in nine of the 16 mummies, but among those who were 45 years or older when they died, atherosclerosis was present in 87%.

The most ancient mummy with evidence of atherosclerosis was Lady Rai, a nursemaid to Queen Amrose Nefertari. Lady Rai died in 1530 BCE at an estimated age of 30 to 40 years; she had definite disease in her aortic arch.

At the AHA last week, Thompson and Wann noted that members of the Egyptian upper classes were meat eaters, and their diets would have included cattle, geese, and ducks. Lack of refrigeration, however, meant that many of these meats would have been heavily salted to prevent spoiling, and this might have led some individuals to develop high blood pressure. Although the exact reasons for the calcified build-up in the arteries is unknown, researchers said the results challenge the view that atherosclerosis is a disease of modern humans.

"This disease has been around since the time of Moses; it's as old as the Pyramids," said Thompson.

The report is also published in the November 18, 2009 issue of the Journal of the American Medical Association.

Live life long and healthy!!

A forwarded email which I think has medical merit.

The top five cancer-causing foods are:

1. Hot dogs
Because they are high in nitrates, the Cancer Prevention Coalition advises that children eat no more than 12 hot dogs a month. If you can't live without hot dogs, buy those made without sodium nitrate.



 
2. Processed meats and bacon
Also high in the same sodium nitrates found in hot dogs, bacon, and other processed meats raise the risk of heart disease. The saturated fat in bacon also contributes to cancer.




3. Doughnuts
Doughnuts are cancer-causing double trouble. First, they are made with white flour, sugar, and hydrogenated oils, then fried at high temperatures. Doughnuts, says Adams , may be the worst food you can possibly eat to raise your risk of cancer.

4. French fries
Like doughnuts, French fries are made with hydrogenated oils and then fried at high temperatures. They also contain cancer- causing acryl amides which occur during the frying process. They should be called cancer fries, not French fries, said Adams .

5. Chips, crackers, and cookies
All are usually made with white flour and sugar. Even the ones whose labels claim to be free of trans-fats generally contain small amounts of trans-fats.






BRAIN DAMAGING HABITS


1. No Breakfast
People who do not take breakfast are going to have a lower blood sugar level.
This leads to an insufficient supply of nutrients to the brain causing brain degeneration.

2. Overeating
It causes hardening of the brain arteries, leading to a decrease in mental power.

3. Smoking
It causes multiple brain shrinkage and may lead to Alzheimer disease.

4. High Sugar consumption
Too much sugar will interrupt the absorption of proteins and nutrients causing malnutrition and may interfere with brain development.

5. Air Pollution
The brain is the largest oxygen consumer in our body. Inhaling polluted air decreases the supply of oxygen to the brain, bringing about a decrease in brain efficiency.

6. Sleep Deprivation
Sleep allows our brain to rest. Long term deprivation from sleep will accelerate the death of brain cells.
7. Head covered while sleeping
Sleeping with the head covered increases the concentration of carbon dioxide and decrease concentration of oxygen that may lead to brain damaging effects.

8. Working your brain during illness
Working hard or studying with sickness may lead to a decrease in effectiveness of the brain as well as damage the brain.


9. Lacking in stimulating thoughts
Thinking is the best way to train our brain, lacking in brain stimulation thoughts may cause brain shrinkage.

10. Talking Rarely
Intellectual conversations will promote the efficiency of the brain



------------------------------ ------------------------------ -------------------------------

The main causes of liver damage are:

1. Sleeping too late and waking up too late are main cause.
2. Not urinating in the morning.
3. Too much eating.
4. Skipping breakfast.
5. Consuming too much medication.
6. Consuming too much preservatives, additives, food coloring, and artificial sweetener.
7. Consuming unhealthy cooking oil. As much as possible reduce cooking oil use when frying, which includes even the best cooking oils like olive oil. Do not consume fried foods when you are tired, except if the body is very fit.
8. Consuming raw (overly done) foods also add to the burden of liver.
Veggies should be eaten raw or cooked 3-5 parts. Fried veggies should be finished in one sitting, do not store.

We should prevent this without necessarily spending more. We just have to adopt a good daily lifestyle and eating habits. Maintaining good eating habits and time condition are very important for our bodies to absorb and get rid of unnecessary chemicals according to 'schedule.'

DO TAKE CARE ABOUT YOUR HEALTH.................

New Joint Statement Streamlines Definition of Metabolic Syndrome

From Heartwire CME

October 12, 2009 — A new joint statement from a number of professional organizations has identified specific criteria for the clinical diagnosis of the metabolic syndrome, tightening up the definition, which previously differed from one organization to the next [1].
The statement, published online October 5, 2009, in Circulation, includes the participation of the International Diabetes Federation (IDF), the National Heart, Lung, and Blood Institute (NHLBI), the World Heart Federation, the International Atherosclerosis Society, and the American Heart Association (AHA) and is an attempt to eliminate some of the confusion regarding how to identify patients with the syndrome.
"This paper represents an attempt to make the definition global," Dr Robert Eckel (University of Colorado, Denver), one of the authors of the new report, told heartwire . "The IDF definition and the [National Cholesterol Education Program Adult Treatment Panel] ATP III definition have been the two that have been utilized most frequently, and now the different organizations--the IDF, the International Atherosclerosis Society, the NHLBI, and the AHA--have all signed on to a single definition. I think that's a step forward in terms of not continuing to confuse people who are working in this field."
Specifically, the new metabolic-syndrome definition streamlines previous differences related to abdominal obesity as defined by measurements in waist circumference. Substantial disparities existed between the previous IDF and the ATP III definitions of what constituted an excessively large waist circumference, by as much as 8 cm between the two groups, but these have been amended. Now, the criteria for elevated waist circumference are based on population- and country-specific definitions, which, although streamlined, do leave some work to be done, said Eckel.
"The problem that still exists is that regional differences around the world may be substantial in terms of what waist circumference confers additional risk for heart disease and diabetes," he said. "The new definition relies on different geographic regions, or different countries, to drill down into their own databases in terms of relating waist circumference to risk." Eckel noted that the IDF previously considered elevations in waist circumference mandatory when defining metabolic syndrome, although the ATP III did not. Now, waist circumference is just one of five criteria that physicians can use when diagnosing the metabolic syndrome. Patients with three of the five criteria--including elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol levels, elevated blood pressure, and elevated fasting-glucose levels--are considered to have the syndrome.

Criteria for Clinical Diagnosis of the Metabolic Syndrome

Measure	Categorical cut points
Elevated waist circumference	Population- and country-specific definitions
Elevated triglycerides (drug treatment for elevated triglycerides is an alternate indicator)	>150 mg/dL
Reduced HDL cholesterol (drug treatment for reduced HDL cholesterol is an alternate indicator)	<40 mg/dL for males and <50 mg/dL for females
Elevated blood pressure (drug treatment for elevated blood pressure is an alternate indicator)	Systolic >130 mm Hg and/or diastolic >85 mm Hg
Elevated fasting glucose (drug treatment for elevated glucose is an alternate indicator)	>100 mg/dL

Notably absent from the joint statement is the American Diabetes Association. As reported by heartwire , there are unresolved scientific issues between the ADA and other associations, including the AHA, regarding the metabolic syndrome. Specifically, the ADA, as well as the European Association for the Study of Diabetes (EASD), objected to the manner in which the metabolic syndrome was characterized as a risk factor for heart disease or diabetes, arguing that there was no need to diagnose a patient with the syndrome because emphasis should be placed on aggressively treating the individual risk factors. In 2005, the ADA and EASD issued their own joint statement calling for a critical appraisal of the metabolic syndrome, its designation as a syndrome, and its clinical utility.
To heartwire , Eckel said the IDF, AHA, NHLBI, and others began working on the new metabolic syndrome definition in 2008 and that they simply went ahead without ADA participation. He stressed the metabolic syndrome is not a disease but simply a clustering of risk factors. The original intention of identifying the syndrome was simply to draw clinicians' and the public's attention to the importance of a high-quality lifestyle, and the metabolic syndrome is never meant to be used as a predictor of heart disease or diabetes risk.

Clinical Context

The metabolic syndrome has received significant attention because of its role in disease. In general, patients with this syndrome exhibit a proinflammatory state, and, in addition to high serum levels of triglycerides and low levels of high-density lipoprotein cholesterol, they tend to have high levels of apolipoprotein B and elevations in small low-density lipoprotein particles. All of these factors contribute to doubling the risk for incident cardiovascular disease within 5 to 10 years as well as a 5-fold increase in the risk for incident type 2 diabetes.
Despite the importance of the metabolic syndrome as a risk marker, there remains disagreement regarding the best way to define it. The current scientific statement attempts to clarify the definition of metabolic syndrome and identifies possible future refinements to this definition.

Study Highlights

• The primary factors used to define the metabolic syndrome have been atherogenic dyslipidemia, elevated blood pressure, and elevated blood glucose levels.
• Whereas some criteria for metabolic syndrome excluded patients with existing type 2 diabetes, current recommendations do not.
• The most significant controversy regarding the definition of the metabolic syndrome has been the inclusion of abdominal obesity. It has been required in some recommendations to diagnose the metabolic syndrome, whereas it has served as a nonintegral variable in the diagnosis in other algorithms.
• Moreover, the definition of abdominal obesity is challenging. Predictive values for various levels of abdominal obesity for cardiovascular disease and diabetes may differ. Different health systems may define abdominal obesity based on more strict or loose criteria to satisfy pragmatic public health or economic concerns.
• Most important, the waist circumference threshold for abdominal obesity varies according to sex and ethnic group. For example, the World Health Organization cutoff values for abdominal obesity for Caucasians are 94 cm or more and 80 cm or more for men and women, respectively. Their respective cutoff values for Asian men and women are 90 cm and 80 cm, and the Japanese Obesity Society defines its respective cutoff values at 85 cm and 90 cm.
• The population-specific method of defining abdominal obesity is also limited by a lack of information from large regions, including the Middle East and Africa.
• At the same time, the use of common diagnostic thresholds across international borders and types of patients will make the diagnosis of metabolic syndrome easier to understand and treat.
• Using recommendations from the different organizations, the authors of the current scientific statement therefore recommend 5 specific criteria and categorical cutoff points to diagnose metabolic syndrome. Patients with at least 3 of these 5 criteria may be considered to have the diagnosis. The criteria are as follows:
  
  • Elevated triglyceride levels or drug treatment of these elevated levels (≥ 150 mg/dL [≥ 1.7 mmol/L])
  • Reduced HDL cholesterol levels or drug treatment of these reduced levels (< 40 mg/dL [1.0 mmol/L] in men; < 50 mg/dL [1.3 mmol/L] in women)
  • Elevated blood pressure or treatment of hypertension (systolic 130 mm Hg and/or diastolic ≥ 85 mm Hg)
  • Elevated fasting glucose levels or treatment with antihyperglycemic medications (≥ 100 mg/dL)
  • Elevated waist circumference (population- and country-specific definitions)
  
  
• New data should emerge, which may help to determine a standard definition for elevated waist circumference, and additional meetings between lead organizations will focus on the development of a single set of diagnostic criteria for metabolic syndrome.

Clinical Implications

• The metabolic syndrome is associated with high levels of apolipoprotein B and increases in small low-density lipoprotein particles as well as a 2-fold increase in the risk for incident cardiovascular disease and a 5-fold increase in the risk for incident type 2 diabetes.
• The current international guidelines set cutoff points for 4 of the 5 criteria that contribute to the diagnosis of metabolic syndrome, but the variability of waist circumference based on sex and race makes a uniform definition for abdominal obesity difficult.

An Overview of the Expanded Definition and Classification of Hypertension Part 5/5

Strategies for and the Clinical Implications of Treating Patients Along a Continuum of Global Cardiovascular Risk

The paradigm shift in viewing elevated BP as a marker for hypertension and hypertension as a progressive CVD syndrome has important implications for treating patients in the clinical setting. The risk-based approach proposed by the HWG will lead to reclassifying patients who were previously designated prehypertensive (based on JNC 7 criteria) to either HWG normal or stage 1 hypertension.^[4] In terms of treatment, lowering BP remains an important goal of antihypertensive therapy, yet ultimately the overarching objective is to prevent CV complications.^[9] Treatment of other CV risk factors is therefore equally important. Moreover, CV risk factors, including elevated BP, are not only precipitators, but also continuous pathogenic components at every stage of progression of CVD.^[9] Clinical strategies, therefore, need to focus on detecting and treating patients at risk at every stage along the continuum, from preventing target-organ damage and interrupting CVD progression in patients with early-stage hypertension, to making aggressive efforts to slow further disease progression and avoid CV events in patients with late-stage hypertension.
Evidence for the benefit of antihypertensive treatment in early-stage hypertension (HWG stage 1 or JNC 7 prehypertension category) has only recently become available. The Trial of Preventing Hypertension (TROPHY) study has shown that antihypertensive therapy may help prevent the development of elevated BP levels among individuals with BP lower than 140/90 mm Hg who are at high risk for frank hypertension (due to the presence of multiple CV risk factors).^[17] In line with the HWG paradigm, patients in this study had high-normal SBP/DBP levels of 130-139/85-89 mm Hg at baseline, yet had a strikingly high rate of CV risk factors other than elevated BP.^[17] Among the TROPHY patients, 96% had at least 1 additional CV risk factor, includingvarious measures of dyslipidemia, insulin resistance, and obesity, as well as elevatedhematocrit and heart rate; 81% had 2 or more additional risk factors; and33% had 4 or more additional risk factors. The most prevalent risk factor in thecohort as being overweight.^[2,17] Patients were randomized to receive treatment with the angiotensin receptor blocker candesartan or placebo for 2 years, followed by an additional 2 years of placebo-only therapy; all patients were instructed to make changes in lifestyle to reduce BP throughout the trial.^[17] After 2 years, hypertension haddeveloped in 154 patients in the placebo group and 53 patients in the angiotensin receptor blockergroup, representing a significant 63% relative risk reduction with pharmacotherapy (P < .001). After 4 years, hypertension had developed in 240 patients assigned to placeboand 208 patients assigned to active treatment (relative risk reduction, 15.6%;P < .007). Serious adverse events occurred in 3.5% of patients who received active treatment and in 5.9% of those who received placebo. As the authors noted, the absolute difference between active treatment and placebo at 2 years in TROPHY, 26.8%, is much higher than the 8% absolute difference observed in the Trials of Hypertension Prevention,^[18] the only trial of lifestyle modification with a similar duration, suggesting that drug therapy plus lifestyle modification is more effective than lifestyle modification alone in early hypertension.^[17]
The benefit of treatment with antihypertensive agents in patients classified as normotensive by conventional standards also is supported by the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).^[19] In this study, antihypertensive treatment in subjects without elevated BP (mean BP, 136/79 mm Hg) but with a history of target-organ damage -- in this case, a history of transient ischemic attacks or stroke -- was associated with a significant 27% reduction in the relative risk for stroke compared with placebo (P < .01), similar to the 32% reduction observed in patients designated as hypertensive.^[19] Moreover, intensive BP reduction with combination therapy was associated with better outcomes than less-intensive BP reduction with single-agent therapy, regardless of hypertension status. Because individuals similar to those considered normotensive in PROGRESS would be classified as having stage 2 hypertension (based on the presence of target-organ damage) in the HWG paradigm, results of this study highlight the importance of considering comprehensive risk factor assessment, including the presence of target-organ damage, when defining and staging patients with hypertension.
Whether all individuals with early-stage hypertension, as defined by the HWG, should be treated with antihypertensive therapy requires further study. As the group emphasized in their 2005 report, characterizing hypertension as a complex CV disorder associated with, but not exclusively defined by, high BP is best viewed as a transitional strategy that is intended to generate further clinical research into improved strategies for detecting, treating, and possibly preventing the disease.^[4]

Summary

The key points advanced by the HWG in their updated hypertension position paper are that BP serves as a biomarker for the disease hypertension and, as such, elevated BP is not synonymous with hypertension. Some individuals may exhibit elevated BP in the absence of hypertension, whereas other individuals with the same levels of BP might be classified into different stages of hypertension.^[6] Therefore, for purposes of calculating total CV risk and staging patients as normal or hypertensive, BP should be evaluated in the context of other CV risk factors and disease markers. Ultimately, it is hoped that the risk-based approach to defining and staging hypertension, as proposed by the HWG, will lead to earlier identification of individuals with hypertensive CVD. Preliminary data, such as that described by the TROPHY Investigators, suggest that lowering BP with pharmacologic therapy can prevent or delay the progression of hypertensive CVD even at early stages (ie, HWG stage 1 hypertension/JNC 7 prehypertension). Additional research is necessary to confirm these findings and identify cost-effective methods to detect and measure early CVD markers in clinical practice.

An Overview of the Expanded Definition and Classification of Hypertension Part 4/5

Clinical Characteristics and Practical Implications of the Proposed Hypertension Categories

A practical clinical interpretation of the revised hypertension categories is shown in Table 6.
Table 6. Clinical Characterization, BP Patterns, and Practical Implications of the Hypertension Algorithm

Hypertension Category	Clinical Characterization	BP Pattern	Practical Implications
Normal	Optimal BP levels	Resting BP levels usually < 120/80 mm Hg	Includes some patients identified as having prehypertension (based on JNC 7 criteria)
	No identifiable early markers of CVD	Occasional BP elevations, even to ≥ 140/90 mm Hg, may occur
Stage 1	Early CVD markers present	BP levels > 115/75 mm Hg	Earliest identifiable stage of hypertensive disease
	Frequently 1 or more CVD risk factors present	BP may be frankly elevated, particularly with environmental stress	Includes individuals with prehypertension (based on JNC 7 criteria) who also have CVD risk factors or early disease markers
	No evidence of target-organ damage
Stage 2	Diffuse disease markers present OR evidence (limited) of early target-organ damage	Sustained resting BP frequently ≥ 140/90 mm Hg, with much higher elevations induced by physiologic or psychologic stressors	Equivalent to JNC 7 stage 1 hypertension
			Indicates progressive disease
			Risk factors, if not attenuated, continue to contribute to progressive target-organ disease
Stage 3	Overt CVD present	Sustained resting BP levels ≥ 140/90 mm Hg usual (untreated or inadequately treated)	Equivalent to JNC 7 stage 2 hypertension
		Marked BP elevations to levels > 160/100 mm Hg not uncommon (untreated or inadequately treated)	Includes all individuals with clinical evidence of overt target-organ damage or CVD, or who have sustained a CVD event, regardless of BP levels

BP = blood pressure; CVD = cardiovascular disease; JNC 7 = Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
In the algorithm, individuals with optimal levels of BP and no identifiable early markers of CVD are categorized as normal. These individuals usually have resting BP levels of 120/80 mm Hg or lower, but BP may be elevated occasionally, even to levels of 140/90 mm Hg or higher.^[6] Given the limits of clinic BP measurements, home BP determinations or 24-hour ambulatory BP recordings may be helpful in identifying patients with more than occasional BP elevations, who may be categorized more appropriately as having stage 1 hypertension.^[16]Because the HWG algorithm does not recognize a prehypertension category, some individuals designated as having prehypertension according to the JNC 7 classification may be considered normal in the paradigm.
The earliest identifiable stage of hypertensive disease, stage 1 hypertension, is characterized by the presence of early CVD markers. Although BP levels are higher than 115/75 mm Hg and may be frankly elevated in patients at this stage, abnormal BP patterns -- including loss of nocturnal dipping, exaggerated responses to exercise or mental stress, and widened pulse pressure -- may provide clearer evidence of the presence of early hypertensive disease.^[4] Although patients should have more than 1 CV risk factor to be included in this category, they should not have any evidence of target-organ damage.
In contrast to stage 1, stage 2 hypertension is characterized by diffuse disease markers and evidence of progressive disease as a consequence of persistent functional and structural changes in BP control mechanisms and in the heart and vasculature. Although patients at this stage frequently have sustained elevations in resting BP levels of 140/90 mm Hg or higher -- with much higher elevations induced by physiologic or psychologic stress -- it is important to recognize that any individual with numerous disease markers or limited evidence of early target-organ damage, such as left ventricular hypertrophy, fits into this category, regardless of BP levels. Methods of detecting or measuring some of the early target-organ damage characteristic of this stage of hypertension are currently limited to specialized or research settings, and further evaluation is needed to determine their potential utility and cost-effectiveness in clinical settings.^[6] Nonetheless, aggressive management of CV risk factors that are identified in patients at this stage may help attenuate the progression of target-organ damage.
Finally, stage 3 hypertension is an advanced stage of the hypertensive continuum, characterized by the presence of overt CVD. Overt hypertensive target-organ disease is often pervasive, and CVD events may have already occurred. If inadequately treated or left untreated, individuals at this stage usually have sustained resting BP levels of 140/90 mm Hg or higher, although marked elevations to levels higher than 160/100 mm Hg are not uncommon.^[6] Regardless of BP levels, however, all individuals with clinical evidence of overt target-organ damage or CVD, as well as those who have already sustained CVD events, are included in this category. Reaching this phase means that damage to target organs, as well as overt cardiorenal disease, has already occurred. As a consequence, CV risk factor modification and treatment of target-organ disease and all identified CVD should be vigorous and sustained.[6

An Overview of the Expanded Definition and Classification of Hypertension Part 3/5

The+Interrelationship+of+High+Blood+Pressure+and+Other+Cardiovascular+Risk+Factors%0D%0A%0D%0AAnother+key+principle+endorsed+by+the+HWG+is+that+of+the+interrelationship+between+elevated+BP+and+other+CV+risk+factors.+Even+in+patients+with+frank+elevations+in+BP%2C+risk+stratification+based+on+BP+levels+alone+often+underestimates+CV+risk.+This+is+because+above-optimal+BP+levels+rarely+occur+in+isolation%2C+and+patients+seen+in+clinical+practice+frequently+have+multiple+CVD+markers+or+risk+factors+%28eg%2C+overweight%2C+insulin+resistance%2C+dyslipidemia%29+that+point+to+greater+overall+risk.%5B1%2C9-13%5D+What+is+particularly+significant%2C+from+the+perspective+of+defining+hypertension+beyond+BP+thresholds%2C+is+that+many+of+these+disease+processes+are+intimately+interrelated+and+interact+via+common+pathobiologic+processes+involving+oxidative+stress+and+endothelial+dysfunction+%28Figure%29.%5B14%5D+Moreover%2C+the+presence+of+risk+factors+and+disease+markers+defines+the+earliest+stage+in+this+CVD+continuum%2C+well+before+overt+CVD+and+target-organ+damage+can+be+measured+in+the+clinic.%5B14%5D+From+this+perspective%2C+above-optimal+BP+%28a+risk+factor%29+is+not+necessarily+synonymous+with+hypertension+%28a+disease+representative+of+progressive+CVD+and+tissue+injury%29.%5B6%5D+%0D%0A%0D%0AAnother+consequence+of+the+CV+and+renal+pathophysiologic+continuum+is+that+the+complex+interplay+of+risk+factors+and+disease+markers+frequently+may+manifest+as+a+dramatically+higher+CV+risk+than+would+be+expected%2C+based+on+thresholds+for+each+individual+risk+factor+alone.+This+is+highlighted+by+the+particularly+deleterious+condition+known+as+the+cardiometabolic+syndrome%2C+in+which+individual+risk+factors+combine+to+increase+CV+risk+synergistically%2C+rather+than+additively.%5B12%2C15%5D+Ultimately%2C+a+more+clinically+meaningful+assessment+of+CV+risk+can+be+obtained+by+global+assessment+of+a+patient%27s+risk%2C+rather+than+focusing+solely+on+whether+a+patient+has+crossed+a+particular+BP+threshold.%0D%0A%0D%0ATaken+together%2C+this+evidence+suggests+that+it+may+be+more+useful+to+view+BP+as+1%2C+but+not+the+only%2C+biomarker+for+the+disease+hypertension%2C+and+to+view+above-optimal+levels+of+BP+in+an+individual+patient+as+those+that%2C+when+sustained%2C+cause+damage+to+the+vasculature.%5B6%5D+This+forms+the+basis+of+the+revised+definition+of+hypertension%2C+as+shown+in+Table+1.%0D%0A%0D%0A%3Cb%3ETable+1.+Revised+Definition+of+Hypertension+From+Hypertension+Writing+Group+2009%3C%2Fb%3E%0D%0A%E2%80%A2+Hypertension+is+a+progressive+CV+syndrome+arising+from+complex+and+interrelated+etiologies%0D%0A%E2%80%A2+Early+markers+of+the+syndrome+are+often+present+before+BP+elevation+is+sustained%3B+therefore%2C+hypertension+cannot+be+classified+solely+by+discreet+BP+thresholds%0D%0A%E2%80%A2+Progression+is+strongly+associated+with+functional+and+structural+cardiac+and+vascular+abnormalities+that+damage+the+heart%2C+kidneys%2C+brain%2C+vasculature%2C+and+other+organs%2C+and+lead+to+premature+morbidity+and+death%0D%0A%E2%80%A2+Reduction+of+elevated+BP+generally+confers+a+reduction+in+the+risk+for+CV+events.+Note+that+HWG+separates+elevated+BP+%28one+manifestation+of+the+disease%29+from+hypertension+%28the+disease%29%0D%0A%0D%0ABP+%3D+blood+pressure%3B+CV+%3D+cardiovascular%0D%0AFrom+Giles+T%2C+et+al.%5B6%5D+%0D%0A%0D%0ABecause+hypertension+is+defined+by+as+%22a+progressive+cardiovascular+syndrome%2C%22+it+is+clinically+helpful+to+categorize%2C+or+stage%2C+patients+%28Table+2%29%2C+with+each+stage+characterized+by+the+cumulative+presence+or+absence+of+markers+of+hypertensive+CVD+and+evidence+of+target-organ+damage.+This+provides+a+snapshot+of+the+extent+to+which+the+disease+has+advanced+at+a+particular+time.%5B6%5D%0D%0A%0D%0A%3Cb%3ETable+2.+Revised+Definition+and+Classification+of+Hypertension+From+Hypertension+Writing+Group+2009%3C%2Fb%3E+++++++++++++++++++++++++%0D%0A%3Ctable+border%3D%221%22+cellpadding%3D%223%22+cellspacing%3D%221%22%3E%3Ctbody%3E%0D%0A%3Ctr+valign%3D%22top%22%3E+++++++++++++++++++++++++++++++++++++%3Ctd%3E%3Cb%3EClassification%3C%2Fb%3E+++++++++++++++++++++++++++++++++++++%0D%0A%3C%2Ftd%3E++++++++++++++++++++++++++++++++++++++%3Ctd%3E%3Cb%3ENormal%3C%2Fb%3E+++++++++++++++++++++++++++++++++++++%0D%0A%3C%2Ftd%3E++++++++++++++++++++++++++++++++++++++%3Ctd%3E%3Cb%3EStage+1+Hypertension%3C%2Fb%3E+++++++++++++++++++++++++++++++++++++%0D%0A%3C%2Ftd%3E++++++++++++++++++++++++++++++++++++++%3Ctd%3E%3Cb%3EStage+2+Hypertension%3C%2Fb%3E+++++++++++++++++++++++++++++++++++++%0D%0A%3C%2Ftd%3E++++++++++++++++++++++++++++++++++++++%3Ctd%3E%3Cb%3EStage+3+Hypertension%3C%2Fb%3E+++++++++++++++++++++++++++++++++++++%0D%0A%3C%2Ftd%3E++++++++++++++++++++++++++++++++++%3C%2Ftr%3E%0D%0A%3Ctr+valign%3D%22top%22%3E+++++++++++++++++++++++++++++++++++++%3Ctd%3EDescriptive+category%0D%0A%3C%2Ftd%3E++++++++++++++++++++++++++++++++++++++%3Ctd+align%3D%22center%22%3ENormal+BP+or+rare+BP+elevations%0D%0AAND%0D%0Ano+identifiable+CVD%0D%0A%3C%2Ftd%3E+++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An Overview of the Expanded Definition and Classification of Hypertension Part 2/5

Blood Pressure as a Biomarker for Hypertension

The concept of elevated BP as a disease marker for hypertension, rather than its cause, is supported by multiple lines of evidence suggesting that the risk for renovascular and CV sequelae may be higher than expected in the presence of normal or near-normal BP in some patients, or, conversely, lower than expected in the presence of above-normal BP in others. This view is based, in part, on the physiologically dynamic nature of BP, in which tissue perfusion is matched with metabolic demands in a complex, ever-changing manner that depends on the coordinated activity of numerous mechanisms involved in hemostasis, including the sympathetic nervous system, the renin-angiotensin system, and the vasodilatory system (eg, prostaglandins and nitric oxide).[4] According to this perspective, optimal BP can vary among individuals and within the same person, depending on hemodynamic circumstances. Sporadic BP elevations may occur in individuals who have no evidence of early CVD.[2] Conversely, because adverse CV and renal outcomes increase across all BP values, hypertension-related morbidity and mortality can occur even at BP levels considered normal by conventional standards. The significant proportions of myocardial infarctions and strokes that occur in patients who have only slight BP elevation, or even normal BP, adds weight to this argument.[7]

Perhaps the most convincing evidence against using BP thresholds to define hypertension is that there is no threshold of BP above 115/70 mm Hg that identifies CV risk -- that is, risk is linear and doubles for each 20/10 mm Hg increase in BP.[2] As a consequence of the dynamic nature of BP, it may be more clinically relevant to use BP patterns, rather than discrete BP thresholds as measured in the clinic, when assessing CV risk in an individual patient. Thus, the HWG places particular attention on ambulatory BP and the contribution of systolic BP (SBP) and pulse pressure (the difference between SBP and diastolic BP [DBP]) to risk, because these are widely considered to be more accurate markers of CV risk than is office DBP, particularly in older patients.[5,8]

An Overview of the Expanded Definition and Classification of Hypertension Part 1/5

For the medical colleagues out there very aching to know all about the NEW JNC 8, these next few posts in the following days are for you..


Introduction

As epidemiologic and clinical data regarding the relationship between blood pressure (BP) and the risk for cardiovascular disease (CVD) have accumulated, a pronounced shift has taken place in how the disease of hypertension is viewed and defined. Cardiovascular (CV) risk has been found to be elevated at BP levels previously considered normal; in some cases, sporadic elevations in BP levels may be physiologically benign and not associated with additional CVD risk.[1-3] As a consequence, many hypertension experts consider elevated BP at its core a disease marker, rather than a cause of hypertension. Moreover, elevated BP, as 1 marker of CVD, frequently coexists with other equally compelling disease markers.[2] Elevated BP should not, therefore, be viewed or treated in isolation, but considered in the context of whole patient care, which takes into account the presence of other risk factors and disease markers for CVD to achieve a more comprehensive, or global, assessment of CV risk.

With these points in mind, in 2005, the Hypertension Writing Group (HWG), a national group of hypertension specialists, proposed a new definition of hypertension as "a progressive cardiovascular syndrome, the early markers of which may be present even before BP elevations are observed."[4] The stated goal of the new definition was to identify individuals at risk for CVD at an earlier point in the disease process, as well as to avoid labeling persons as hypertensive who are at low risk for CVD.[4] Viewed from this perspective, the HWG believed that threshold-based classification systems of hypertension, such as that endorsed in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7),[5] while serving as tools to identify patients across a broad range of CVD risk, may lead to underestimation or overestimation of clinical risk within individual patients. In either case, the presence or absence of other disease markers or risk factors, the coexistence of target-organ damage, or both can be used to risk-stratify patients with hypertension more accurately.

To simplify risk stratification and align it more closely with clinical practice, the HWG proposed classifying all patients as either normal or hypertensive (eliminating the prehypertension category proposed in JNC 7), with hypertension classified into stage 1, stage 2, or stage 3.[4] Because the CV syndrome represented by hypertension may be present even when BP falls within the normal category by conventional standards, the risk categories created by the HWG focus not on BP levels per se, but on the presence of deleterious BP patterns or the presence of CVD. Stages of hypertension are further categorized based on the presence of risk factors for early, advanced, or progressive CVD, as well as by other CVD markers (classified as BP, cardiac, vascular, renal, and retinal changes) and target-organ damage (classified as cardiac, vascular, renal, and cerebrovascular).[4]

Beyond the goal of providing a more clinically relevant assessment of global CV risk in clinical practice, this paradigm shift served to focus attention on the enormous unmet need regarding prevention and optimal treatment of hypertension across a spectrum of fields, from basic research and drug development to patient education and clinical management.[4] Two critical areas of research in particular -- the development of specific and sensitive cost-effective tests that can detect early CVD markers in the clinical setting, and the development of strategies to slow or prevent the onset of target-organ damage or overt CVD by treating early vascular derangements -- may benefit from being examined within the context of the categories for hypertension.

Recently, the HWG further refined and updated the definition and classification of hypertension.[6] This article reviews the revised definition and classification scheme and the implications for clinical practice. As the authors stressed, however, while definitions of disease are useful for detection, management, research, and education, definitions alone do not constitute recommendations for treatment. In the latter case, the initiation of treatment should be individualized and guided by CV risk, rather than BP thresholds.[1]

Warfarin Use in Patients With End-Stage Renal Disease May Increase Stroke Risk

If you happen to be taking coumadin and had been told that you also have kidney disease, this should be read...

September 3, 2009 — Use of warfarin as chemoprophylaxis in patients with atrial fibrillation and end-stage renal disease (ESRD) may paradoxically increase stroke risk, according to the results of a cohort study reported in the August 27 Online First issue of the Journal of the American Society of Nephrology.

"Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities," write Kevin E. Chan, MD, from Fresenius Medical Care NA in Waltham, Massachusetts, and colleagues. "We previously reported a significant excess mortality associated with anticoagulation and/or antiplatelet use in a large, heterogeneous population of incident hemodialysis (HD) patients."

The purpose of this follow-up study was to evaluate the potential risk-benefit ratio of warfarin, clopidogrel, and aspirin specifically in dialysis patients with coexisting atrial fibrillation. The investigators looked at the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort of 1671 patients with preexisting atrial fibrillation who were receiving hemodialysis. Average follow-up of patient outcomes was 1.6 years from the time dialysis was started.

Patients receiving warfarin therapy had a significantly increased risk for new stroke vs patients not taking warfarin (hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.29 - 2.90). Risk for new stroke was not associated with clopidogrel or aspirin use.

There appeared to be a dose-response relationship between the degree of anticoagulation and new stroke in patients receiving warfarin, based on an analysis using international normnormed ratio (INR; P = .02 for trend). Compared with nonusers of warfarin, those users who had no INR monitoring in the first 90 days of dialysis had the highest risk for stroke (HR, 2.79; 95% CI, 1.65 - 4.70). Use of warfarin was not statistically significantly associated with any increases in all-cause mortality or hospitalization rates.

"Warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke," the study authors write. "The risk is greatest in warfarin users who do not receive in-facility INR monitoring."

Limitations of this study include retrospective design, potential misclassification bias, confounding by indication, survivorship bias, ascertainment bias, and selection bias from missing data.

"Before definitive conclusions can be drawn, large, prospective, randomized, controlled trials are required," the study authors conclude. "Until then, physicians should be cognizant of the possible risks associated with warfarin use for atrial fibrillation in patients with ESRD, with careful evaluation of the risks and benefits of intervention at the individual patient level. Close monitoring of the degree of anticoagulation (INR) in patients who are on warfarin would also be a reasonable recommendation to minimize the risk for hemorrhagic complications."

Music Therapy Lowers Blood Pressure and Reduces Reinfarction Rates in ACS

Some article to back up old anti stress therapy for the one with sick heart...

September 4, 2009 (Barcelona, Spain) – Music might be good for the soul, but a study presented this week suggests it could also be associated with more tangible cardiovascular benefits.

Researchers here at the European Society of Cardiology 2009 Congress showed that music therapy reduced blood pressure, heart rate, and patient anxiety and had a significant effect on future events, including reinfarction and sudden death, in acute coronary syndrome patients who underwent revascularization.

Speaking with heartwire , lead investigator Dr Predrag Mitrovic (University of Belgrade, Serbia) said previous studies have shown that music therapy can have positive effects on the heart, namely by decreasing sympathetic nervous activity. Other reports, including a study reported previously by heartwire , have shown that the positive emotions aroused by happy, joyful music can have favorable effects on the endothelium.

In this study, Mitrovic and colleagues provide data on their seven-year experience with using music therapy in patients with acute coronary syndrome who had undergone revascularization. In total, 740 patients between April 1990 and January 2009 were included in the analysis, with 370 patients receiving two sessions of music therapy for 12 minutes daily and 370 patients not listening to music.

During the seven-year follow-up period, patients who listened to music had less anxiety, although the score did not reach statistical significance, and statistically significant reductions in systolic and diastolic blood pressures and heart rate. Patients who listened to music also had significantly less angina, less heart failure, and lower rates of reinfarction, sudden death, and revascularization.

Mitrovic said the music preferred by patients is typically classical but that they are not always up front, at least at first, about their musical preferences. "A lot of patients don't want to tell us the truth about the type of music they like," said Mitrovic. "Some of them like national music, and they don't like to tell us about it. But if we give them the wrong type of music, it might have a negative effect."

The group hopes to publish the study shortly, but in the meantime it recommends music therapy in acute coronary syndrome patients who have undergone revascularization as an inexpensive means to lower the stress and emotional disturbance they might feel worrying about a second event.

Role of the A1c Assay in the Diagnosis of Diabetes (part 1)

Abstract

An International Expert Committee with members appointed by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation was convened in 2008 to consider the current and future means of diagnosing diabetes in nonpregnant individuals. The report of the International Expert Committee represents the consensus view of its members and not necessarily the view of the organizations that appointed them. The International Expert Committee hopes that its report will serve as a stimulus to the international community and professional organizations to consider the use of the A1C assay for the diagnosis of diabetes.


Introduction

Diabetes is a disease characterized by abnormal metabolism, most notably hyperglycemia, and an associated heightened risk for relatively specific long-term complications affecting the eyes, kidney, and nervous system. Although diabetes also substantially increases the risk for cardiovascular disease, cardiovascular disease is not specific to diabetes and the risk for cardiovascular disease has not been incorporated into previous definitions or classifications of diabetes or of subdiabetic hyperglycemia.

Can the A1C Test Be Used to Diagnose Diabetes?

If chronic hyperglycemia sufficient to cause diabetes-specific complications is the hallmark of diabetes, common sense would dictate that laboratory measures that capture long-term glycemic exposure should provide a better marker for the presence and severity of the disease than single measures of glucose concentration. Observational studies that have assessed glycemia with measures that capture longer-term exposure (i.e., A1C) or with single or longitudinal measurements of glucose levels have consistently demonstrated a strong correlation between retinopathy and A1C[24-26] but a less consistent relationship with fasting glucose levels.[27] In one study that measured both FPG and A1C, there was a stronger correlation between A1C and retinopathy than between fasting glucose levels and retinopathy.[25] The correlation between A1C levels and complications has also been shown in the setting of controlled clinical trials in type 1[28] and type 2[29] diabetes, and these findings have been used to establish the widely accepted A1C treatment goals for diabetes care.[30]

All of these observations suggest that a reliable measure of chronic glycemic levels such as A1C, which captures the degree of glucose exposure over time[31,32] and which is related more intimately to the risk of complications than single or episodic measures of glucose levels, may serve as a better biochemical marker of diabetes and should be considered a diagnostic tool. Although the 1997 expert committee report considered this option, it recommended against using A1C values for diagnosis in part because of the lack of assay standardization.[17] The 2003 follow-up report noted that, while the National Glycohemoglobin Standardization Program [33] had succeeded in standardizing the vast majority of assays used in the U.S., the use of A1C for diagnosis still had "disadvantages," and it reaffirmed the previous recommendation that A1C not be used to diagnose diabetes.[21]

An updated examination of the laboratory measurements of glucose and A1C by the current International Expert Committee indicates that with advances in instrumentation and standardization, the accuracy and precision of A1C assays at least match those of glucose assays. The measurement of glucose itself is less accurate and precise than most clinicians realize.[34] A recent analysis of the performance of a variety of clinical laboratory instruments and methods that measure glucose revealed that 41% of instruments have a significant bias from the reference method that would result in potential misclassification of >12% of patients.[35] There are also potential preanalytic errors owing to sample handling and the well-recognized lability of glucose in the collection tube at room temperature.[36,37] Even when whole blood samples are collected in sodium fluoride to inhibit in vitro glycolysis, storage at room temperature for as little as 1 to 4 h before analysis may result in decreases in glucose levels by 3-10 mg/dl in nondiabetic individuals.[36-39]

By contrast, A1C values are relatively stable after collection,[40] and the recent introduction of a new reference method to calibrate all A1C assay instruments should further improve A1C assay standardization in most of the world.[41-43] In addition, between- and within-subject coefficients of variation have been shown to be substantially lower for A1C than for glucose measurements.[44] The variability of A1C values is also considerably less than that of FPG levels, with day-to-day within-person variance of <2% for A1C but 12-15% for FPG.[45-47] The convenience for the patient and ease of sample collection for A1C testing (which can be obtained at any time, requires no patient preparation, and is relatively stable at room temperature) compared with that of FPG testing (which requires a timed sample after at least an 8-h fast and which is unstable at room temperature) support using the A1C assay to diagnose diabetes.

In summary, compared with the measurement of glucose, the A1C assay is at least as good at defining the level of hyperglycemia at which retinopathy prevalence increases; has appreciably superior technical attributes, including less preanalytic instability and less biologic variability; and is more clinically convenient. A1C is a more stable biological index than FPG, as would be expected with a measure of chronic glycemia levels compared with glucose concentrations that are known to fluctuate within and between days ( Table 1 ).

Table 1. Advantages of A1C Testing Compared With FPG or 2HPG for the Diagnosis of Diabetes

* Standardized and aligned to the DCCT/UKPDS; measurement of glucose is less well standardized
* Better index of overall glycemic exposure and risk for long-term complications
* Substantially less biologic variability
* Substantially less preanalytic instability
* No need for fasting or timed samples
* Relatively unaffected by acute (e.g., stress or illness related) perturbations in glucose levels
* Currently used to guide management and adjust therapy

CDC Guidelines for Use of Influenza A (H1N1) 2009 Monovalent Vaccine

August 27, 2009 — The US Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) has issued guidelines regarding the use of vaccine against infection with novel influenza A (H1N1) virus. The new recommendations were posted online August 21 in the Morbidity and Mortality Weekly Report.

"Because novel influenza A (H1N1) virus is continuing to cause illness in the United States and worldwide, the primary focus of vaccination efforts should be to vaccinate as many persons as possible in the recommended target groups as quickly as possible once vaccine becomes available," write Anne Schuchat, MD, and colleagues from the National Center for Immunization and Respiratory Diseases, CDC.

H1N1 Vaccine Use

"As vaccine availability increases, additional groups are recommended for vaccination.... These recommendations are intended to provide vaccination programs and providers with information to assist in planning and to alert providers and the public about target groups comprising an estimated 159 million persons who are recommended to be first to receive influenza A (H1N1) 2009 monovalent vaccine," write Dr. Schuchat and colleagues.

To assess which population groups should first be targeted for vaccination, the ACIP reviewed epidemiologic and clinical data on July 29, 2009. The ACIP also evaluated the projected supply likely to be available when the vaccine first becomes available, as well as the anticipated increase in vaccine availability during the following 6 months. By mid-October 2009, it is anticipated that licensed H1N1 vaccine will be available.

The guidelines recommend that vaccination efforts begin as soon as the vaccine is available. In accordance with state and local conditions, state and local health officials and vaccination providers should make decisions concerning vaccine administration and distribution.

Vaccination and healthcare providers should be vigilant about following announcements and other information forthcoming from state and local health departments and the CDC regarding vaccination against H1N1 virus infection. The CDC's influenza Web site and state and local health departments may provide additional information.

ACIP H1N1 Vaccine Recommendations

Key points of the ACIP recommendations include the following 3 items.

* First, 5 general population groups that should be targeted as an initial focus of vaccination efforts are pregnant women, household contacts or caregivers for infants younger than 6 months (such as parents, siblings, and daycare providers), healthcare and emergency medical services personnel, children and young adults 6 months to 24 years of age, and persons aged 25 to 64 years who are at greater risk for influenza-related complications because of underlying medical conditions. These medical conditions increasing risk for influenza-related complications include chronic pulmonary conditions, including asthma; cardiovascular conditions except for hypertension; renal, hepatic, cognitive, neurologic/neuromuscular, hematologic, or metabolic disorders, including diabetes mellitus; and immunosuppression caused by medications or by human immunodeficiency virus.
* Second, if initial vaccine availability is insufficient to meet demand, priority is established for a subset of persons within the initial target groups. These persons who are to receive priority for vaccination (order of target groups does not indicate priority) include pregnant women, household contacts or caregivers for infants younger than 6 months, healthcare and emergency medical services personnel in direct contact with patients or infectious material, children 6 months to 4 years of age, and children and adolescents aged 5 to 18 years who are at greater risk for influenza-related complications because of underlying medical conditions.
* Third, as vaccine availability increases, other adult population groups should receive H1N1 vaccine in accordance with the guidelines recommendations.

In addition, ACIP made additional recommendations concerning the use of influenza A (H1N1) 2009 monovalent vaccine, as follows:

* The number of doses of vaccine needed for immunization against H1N1 has not been determined. Vaccine should not be stockpiled for patients who already have received 1 dose but might require a second dose, because vaccine availability is expected to increase over time.
* If different anatomic sites are used, inactivated vaccines against seasonal and H1N1 viruses may be administered simultaneously. However, ACIP does not recommend simultaneous administration of live, attenuated vaccines against seasonal and H1N1 virus.
* All persons, including those older than 65 years of age, who are currently recommended for seasonal influenza vaccine should receive the seasonal vaccine as soon as it is available. Recommendations for use of the 2009 to 2010 seasonal influenza vaccine were previously published.

"The guiding principle of these recommendations is to vaccinate as many persons as possible as quickly as possible," the guidelines authors state."ACIP will review new epidemiologic and clinical data as they become available and might revise these recommendations."

Morb Mortal Wkly Rep. Published online August 21, 2009.

WHO Guidelines for Antiviral Treatment for H1N1 and Other Influenza

August 25, 2009 — The World Health Organization (WHO) has issued guidelines for antiviral treatment for novel influenza A (H1N1) and other influenza. The purpose of the new recommendations, which were posted online August 20, is to provide a basis for advice to clinicians regarding the use of the currently available antivirals for patients presenting with illness caused by influenza virus infection, as well as considerations regarding potential use of these antiviral medications for chemoprophylaxis.

On the basis of a review of data collected with previously circulating strains, and treatment of human H5N1 influenza virus infections, the new guidelines expand on recommendations published in May 2009, titled ʺClinical management of human infection with new influenza A (H1N1) virus: Initial guidance." These new guidelines do not change recommendations in the WHO rapid advice guidelines on pharmacological management of humans infected with highly pathogenic avian influenza A (H5N1) virus.

"In April 2009, the [WHO] received reports of sustained person to person infections with [H1N1] virus in Mexico and the United States," write Edgar Bautista, from Médico Neumólogo Intensivista, Jefe de UCI-INER in Mexico, and colleagues. "Subsequent international spread led WHO to declare on 11 June 2009 that the first influenza pandemic in 41 years had occurred. This 2009 pandemic H1N1 influenza virus has now spread worldwide, with confirmed cases of pandemic H1N1 virus infection reported in more than 100 countries in all 6 WHO regions[, which] has led to the need to add to the existing guidance on the use of antivirals."

The new recommendations highlight oseltamivir and zanamivir, which are neuraminidase inhibitors, and amantadine and rimantadine, which are M2 inhibitors. Suggestions are also provided regarding the use of some other potential pharmacological treatments, such as ribavirin, interferons, immunoglobulins, and corticosteroids.

Management of patients with pandemic influenza (H1N1) 2009 virus infection is the primary focus of the statement, although it also includes guidance regarding the use of the antivirals for treatment of other seasonal influenza virus strains, as well as for infections resulting from novel influenza A virus strains.

The guidelines urge country and local public health authorities to issue local recommendations for clinicians periodically, based on epidemiological and antiviral susceptibility data on the locally circulating influenza strains. As the prevalence and severity of the current pandemic evolves, WHO anticipates that additional data will be forthcoming that may require revision of the current recommendations. WHO therefore plans to review the guidance no later than September 2009 to determine whether modifications to the recommendations are needed.

Recommendations for Antiviral Treatment of H1N1

For patients with confirmed or strongly suspected infection with influenza pandemic (H1N1) 2009, when antiviral medications for influenza are available, specific recommendations regarding use of antivirals for treatment of pandemic (H1N1) 2009 influenza virus infection are as follows:

* Oseltamivir should be prescribed, and treatment started as soon as possible, for patients with severe or progressive clinical illness (strong recommendation, low-quality evidence). Depending on clinical response, higher doses of up to 150 mg twice daily and longer duration of treatment may be indicated. This recommendation is intended for all patient groups, including pregnant women, neonates, and children younger than 5 years of age.
* Zanamivir is indicated for patients with severe or progressive clinical illness when oseltamivir is not available or not possible to use, or when the virus is resistant to oseltamivir but known or likely to be susceptible to zanamivir (strong recommendation, very low quality evidence).
* Antiviral treatment is not required in patients not in at-risk groups who have uncomplicated illness caused by confirmed or strongly suspected influenza virus infection (weak recommendation, low-quality evidence). Patients considered to be at risk are infants and children younger than 5 years of age; adults older than 65 years of age; nursing home residents; pregnant women; patients with chronic comorbid disease including cardiovascular, respiratory, or liver disease and diabetes; and immunosuppressed patients because of malignancy, HIV infection, or other diseases.
* Oseltamivir or zanamivir treatment should be started as soon as possible after the onset of illness in patients in at-risk groups who have uncomplicated illness caused by influenza virus infection (strong recommendation, very low quality evidence).

Recommendations for Chemoprophylaxis of H1N1

Specific recommendations regarding the use of antivirals for chemoprophylaxis of pandemic (H1N1) 2009 influenza virus infection are as follows:

* When risk for human-to-human transmission of influenza is high or low, and the probability of complications of infection is high, either because of the influenza strain or because of the baseline risk of the exposed group, use of oseltamivir or zanamivir may be considered as postexposure chemoprophylaxis for the affected community or group, for individuals in at-risk groups, or for healthcare workers (weak recommendation, moderate-quality evidence).
* Individuals in at-risk groups or healthcare personnel need not be offered antiviral chemoprophylaxis if the likelihood of complications of infection is low. This recommendation should be applied independent of risk for human-to-human transmission (weak recommendation, low-quality evidence).

For treatment of mild to moderate uncomplicated clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities, patients in at-risk groups should be treated with zanamivir or oseltamivir plus M2 inhibitor (noting that amantadine should not be used in pregnant women). Otherwise-healthy patients with this presentation need not be treated.

When the clinical presentation of infection with multiple cocirculating influenza A subtypes or viruses with different antiviral susceptibilities is severe or progressive, all patients should be treated with oseltamivir plus M2 inhibitor, or zanamivir.

For treatment of mild to moderate uncomplicated clinical presentation of infection with sporadic zoonotic influenza A viruses including H5N1, the at-risk population should be treated with oseltamivir or zanamivir, and the otherwise-healthy population with oseltamivir. All patients, regardless of risk status, with severe or progressive presentation of infection with sporadic zoonotic influenza A viruses including H5N1 should be treated with oseltamivir plus an M2 inhibitor.

WHO Rapid Advice Guidelines on Pharmacological Management of Influenza Virus. Published online August 20, 2009.

Interim Guidance on Antiviral Recommendations for Patients with Novel Influenza A (H1N1) Virus Infection and Their Close Contacts

Objective: To provide updated interim guidance on the use of antiviral agents for treatment and chemoprophylaxis of novel influenza (H1N1) virus infection, and assist clinicians in prioritizing use of antivirals for treatment or chemoprophylaxis of patients at higher risk for influenza-related complications. Additional revisions to these recommendations for antiviral treatment should be expected as the epidemiology and clinical presentation of novel influenza A (H1N1) virus infection is better understood. This guidance can be adapted according to local epidemiologic data and antiviral supply considerations.

High-risk groups: A person who is at high-risk for complications of novel influenza (H1N1) virus infection is defined as the same for seasonal influenza at this time. As more epidemiologic and clinical data become available, these risk groups might be revised.

• Children younger than 5 years old. The risk for severe complications from seasonal influenza is highest among children younger than 2 years old.
• Adults 65 years of age and older.
• Persons with the following conditions:
• Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus);
• Immunosuppression, including that caused by medications or by HIV;
• Pregnant women;
• Persons younger than 19 years of age who are receiving long-term aspirin therapy;
• Residents of nursing homes and other chronic-care facilities.

Transmission: Transmission of novel influenza A (H1N1) is being studied as part of the ongoing outbreak investigation, but limited data available indicate that this virus is likely transmitted in ways similar to other influenza viruses. Seasonal human influenza viruses are thought to be transmitted between persons primarily through large-particle respiratory droplet transmission (e.g., when an infected person coughs or sneezes near a susceptible person). Transmission via these large-particle droplets requires close contact between source and recipient persons because droplets do not remain suspended in the air and generally travel only a short distance (<>

Close contact, for the purposes of this document, is defined as having cared for or lived with a person who is a confirmed, probable or suspected case of novel influenza A (H1N1), or having been in a setting where there was a high likelihood of contact with respiratory droplets and/or body fluids of such a person. Examples of close contact include kissing or embracing, sharing eating or drinking utensils, physical examination, or any other contact between persons likely to result in exposure to respiratory droplets. Close contact typically does not include activities such as walking by an infected person or sitting across from a symptomatic patient in a waiting room or office.

Special Considerations for Children
Aspirin or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) should not be administered to any confirmed or suspected ill case of novel influenza H1N1 virus infection aged 18 years old and younger due to the risk of Reye syndrome. For relief of fever, other anti-pyretic medications such as acetaminophen or non- steroidal anti-inflammatory drugs are recommended.

Children younger than 4 years of age should not be given over-the-counter cold medications without first speaking with a healthcare provider.

Antiviral Resistance

This novel (H1N1) influenza virus is sensitive (susceptible) to the neuraminidase inhibitor antiviral medications, zanamivir and oseltamivir. It is resistant to the adamantane antiviral medications, amantadine and rimantadine.

Antiviral Treatment for Novel (H1N1) Influenza

For antiviral treatment of novel influenza (H1N1) virus infection, either oseltamivir or zanamivir are recommended. Recommendations for use of antivirals may change as data on antiviral effectiveness, clinical spectrum of illness, adverse events from antiviral use, and antiviral susceptibility data become available.

Clinical judgment is an important factor in treatment decisions. Persons with suspected novel H1N1 influenza who present with an uncomplicated febrile illness typically do not require treatment unless they are at higher risk for influenza complications, and in areas with limited antiviral mediation availability, local public health authorities might provide additional guidance about prioritizing treatment within groups at higher risk for infection.

Treatment is recommended for:

1. All hospitalized patients with confirmed, probable or suspected novel influenza (H1N1).
2. Patients who are at higher risk for seasonal influenza complications (see above).

If a patient is not in a high-risk group or is not hospitalized, healthcare providers should use clinical judgment to guide treatment decisions, and when evaluating children should be aware that the risk for severe complications from seasonal influenza among children younger than 5 years old is highest among children younger than 2 years old. Many patients who have had novel influenza (H1N1) virus infection, but who are not in a high-risk group have had a self-limited respiratory illness similar to typical seasonal influenza. For most of these patients, the benefits of using antivirals may be modest. Therefore, testing, treatment and chemoprophylaxis efforts should be directed primarily at persons who are hospitalized or at higher risk for influenza complications.

Once the decision to administer antiviral treatment is made, treatment with zanamivir or oseltamivir should be initiated as soon as possible after the onset of symptoms. Evidence for benefits from antiviral treatment in studies of seasonal influenza is strongest when treatment is started within 48 hours of illness onset. However, some studies of oseltamivir treatment of hospitalized patients with seasonal influenza have indicated benefit, including reductions in mortality or duration of hospitalization even for patients whose treatment was started more than 48 hours after illness onset. Recommended duration of treatment is five days. Antiviral doses recommended for treatment of novel H1N1 influenza virus infection in adults or children 1 year of age or older are the same as those recommended for seasonal influenza .

Oseltamivir use for children <1>

Note: Areas that continue to have seasonal influenza activity, especially those with circulation of oseltamivir-resistant seasonal human influenza A (H1N1) viruses, might prefer to use either zanamivir or a combination of oseltamivir and rimantadine or amantadine to provide adequate empiric treatment or chemoprophylaxis for patients who might have seasonal human influenza A (H1N1) virus infection.

Antiviral Chemoprophylaxis for Novel (H1N1) Influenza

For antiviral chemoprophylaxis of novel (H1N1) influenza virus infection, either oseltamivir or zanamivir are recommended (Table 1). Duration of antiviral chemoprophylaxis post-exposure is 10 days after the last known exposure to novel (H1N1) influenza. The indication for post-exposure chemoprophylaxis is based upon close contact with a person who is a confirmed, probable or suspected case of novel influenza A (H1N1) virus infection during the infectious period of the case. The infectious period for persons infected with the novel influenza A (H1N1) virus is assumed to be similar to that observed in studies of seasonal influenza. With seasonal influenza, studies have shown that people may be able to transmit infection beginning one day before they develop symptoms to up to 7 days after they get sick. Children, especially younger children, might potentially be infectious for longer periods. However, for this guidance, the infectious period is defined as one day before until 7 days after the case’s onset of illness. If the contact occurred with a case whose illness started more than 7 days before contact with the person under consideration for antivirals, then chemoprophylaxis is not necessary. For pre-exposure chemoprophylaxis, antiviral medications should be given during the potential exposure period and continued for 10 days after the last known exposure to a person with novel (H1N1) influenza virus infection during the cases infectious period. Oseltamivir can also be used for chemoprophylaxis under the EUA for children less than 1 year of age (see Children Under 1 Year of Age).

Post exposure antiviral chemoprophylaxis with either oseltamivir or zanamivir can be considered for the following:

1. Close contacts of cases (confirmed, probable, or suspected) who are at high-risk for complications of influenza
2. Health care personnel, public health workers, or first responders who haves had a recognized, unprotected close contact exposure to a person with novel (H1N1) influenza virus infection (confirmed, probable, or suspected) during that person’s infectious period. Information on appropriate personal protective equipment is available at: Interim Guidance for Infection Control for Care of Patients with Confirmed or Suspected Swine Influenza A (H1N1) Virus Infection in a Healthcare Setting and might be updated frequently as additional information on transmission becomes available.

Pre-exposure antiviral chemoprophylaxis should only be used in limited circumstances, and in consultation with local medical or public health authorities. Certain persons at ongoing occupational risk for exposure who are also at higher risk for complications of influenza (e.g., health care personnel, public health workers, or first responders who are working in communities with influenza A H1N1 outbreaks) should carefully follow guidelines for appropriate personal protective equipment or consider temporary reassignment.

Antiviral Use for Control of Novel H1N1 Influenza Outbreaks

Use of antiviral drugs for treatment and chemoprophylaxis of influenza has been a cornerstone for the control of seasonal influenza outbreaks in nursing homes and other long term care facilities.

At this time, no outbreaks of novel influenza A (H1N1) have been reported in such settings. However, if such outbreaks were to occur, it is recommended that ill patients be treated with oseltamivir or zanamivir and that chemoprophylaxis with either oseltamivir or zanamivir be started as early as possible to reduce the spread of the virus as is recommended for seasonal influenza outbreaks in such settings.

Chemoprophylaxis should be administered to all non-ill residents and should continue for a minimum of 2 weeks. If surveillance indicates that new cases continue to occur, chemoprophylaxis should be continued until approximately 7 days after illness onset in the last patient. In addition to antiviral medications, other outbreak-control measures include appropriate infection control, establishing cohorts of patients with confirmed or suspected influenza, restricting staff movement between wards or buildings, and restricting contact between ill staff or visitors and patients, and active surveillance for new cases. Medical directors of long-term care facilities should review their plans for outbreak control of influenza.

In addition to use in nursing homes, antiviral chemoprophylaxis also can be considered for controlling influenza outbreaks in other closed or semiclosed settings (e.g., correctional facilities, or other settings in which persons live in close proximity.

Table 1. Antiviral medication dosing recommendations for treatment or chemoprophylaxis of novel influenza A (H1N1) infection. (Table extracted from IDSA guidelines for seasonal influenza.)
Agent, group		Treatment	Chemoprophylaxis
Oseltamivir
Adults		75-mg capsule twice per day for 5 days	75-mg capsule once per day
Children ≥ 12 months	15 kg or less	60 mg per day divided into 2 doses	30 mg once per day
	15-23 kg	90 mg per day divided into 2 doses	45 mg once per day
	24-40 kg	120 mg per day divided into 2 doses	60 mg once per day
	>40 kg	150 mg per day divided into 2 doses	75 mg once per day
Zanamivir
Adults		Two 5-mg inhalations (10 mg total) twice per day	Two 5-mg inhalations (10 mg total) once per day
Children		Two 5-mg inhalations (10 mg total) twice per day (age, 7 years or older)	Two 5-mg inhalations (10 mg total) once per day (age, 5 years or older)