Online newspaper of professor Yasser Metwally

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

NEW YORK (Reuters Health) Mar 21 - Mild traumatic brain injury (mTBI) is often followed by acute post-concussion syndrome but does not predict the condition, according to Australian researchers.

Investigator Dr. E. Arthur Shores told Reuters Health that these results are similar to findings by other investigators who studied military personnel after combat. “Once post-traumatic stress disorder and depression was considered, the effect of mTBI was non-significant,” Dr. Shores said.

He added, “Post-concussion syndrome has been a controversial diagnosis in both civilian and military populations.”

In the March issue of the Journal of Neurology, Neurosurgery and Psychiatry, Dr. Shores of Macquarie University, Sydney and colleagues note that they evaluated 175 trauma patients — 90 with mTBI and 85 without brain injury - for symptoms including poor concentration, irritability, memory problems, and mood swings. Subjects were analyzed with a modified Post-Concussion Syndrome Checklist, along with validated psychological and neuropsychological tests.

According to the report, 43.3% of mTBI patients and 43.5% of controls met the criteria for diagnosis of acute post-concussion syndrome. The strongest effect was seen in those who had had a previous affective or anxiety disorder (odds ratio 5.76). Women were at more than a 3-fold greater risk than men.

“For individuals who have mTBI,” Dr. Shores, concluded, “it is important they know that symptoms they continue to experience are not due to brain injury. They can be treated with early education and psychological therapies.”

In an accompanying editorial, Dr. Graham E. Powell of Powell Campbell Edelmann in London, points out the importance of taking into account the fact that some symptoms “have a high base rate of occurrence in the general population.” He emphasizes that post-concussion syndrome symptoms “are rife in the general population,” adding that this high base rate can lead to diagnoses which “will often be plain wrong.”

References

1. J Neurol Neurosurg Psychiatry 2008;79:237,300-306.

2. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

March 31, 2008 — Poststroke depression prevents almost as many stroke survivors from returning to work as physical disability, new research suggests.

Investigators from the George Institute for International Health, in Sydney, Australia, found that among stroke survivors who had paying jobs in the month prior to their stroke, psychiatric morbidity 28 days poststroke was associated with a significantly lower likelihood of returning to work, second only to physical disability.

“Employment is a key determinant of one’s role in society, and psychiatric morbidity is a major cause for poor work performance and absence from the workforce,” the authors write.

Further, the study showed that only 30% of patients with poststroke depression reported having any treatment for it at 6-month follow-up.

Led by Nick Glozier, MD, PhD, the study is published online March 27 in Stroke.

• Social Impact of Stroke Overlooked

According to the paper, despite the fact that up to 20% of strokes occur in relatively young people of working age, few studies have looked at determinants of returning to paid work following stroke.

“A striking number of people have strokes when they are of working age, and returning to employment is vital to their well-being and to their role in society. Since younger adults have responsibilities for generating an income and supporting family members, returning to work is a key goal in recovery,” Dr. Glozier said in a statement from the American Stroke Association.

To determine the frequency of returning to work and its predictors, the investigators used data from the third Auckland Regional Community Stroke (ARCOS) study, a prospective, population-based study that examined outcomes of stroke survivors who were alive at least 6 months after a first stroke.

One week after their stroke, patients were assessed using the Barthel Index (BI) to determine their ability to independently perform basic self-care and activities of daily living.

At 28-day follow-up, patients’ psychiatric status was assessed using the 28-item General Health Questionnaire (GHQ-28). Study subjects were followed up again at 6 months.

• Need for Greater Attention

Among 1423 patients registered with first-ever strokes, 279 (20%) had been previously employed before their event. Of these, 55 died before 28 days, 24 were not cognitively competent at the 28-day interview, and 36 were either unavailable or refused to participate, leaving 164 who had a GHQ-28 assessment at 1 month.

A total of 210 previously employed patients survived to 6 months and, of these, 112 (53%) returned to work following acute stroke.

According to the study, the strongest predictor of not returning to work was physical disability. Of those working at 6 months, 71% had been rated as independent on the BI. In contrast, among those who did not return to work only 32% been deemed physically independent.

Of those working 6 months after stroke, 33% had poststroke depression vs 45% of those who were not working. According to the study, patients were more likely to have poststroke depression if they were younger, had a more severe stroke, or had previously been treated for depression.

According to the investigators, the study highlights the need for greater attention to be paid to psychiatric morbidity in stroke patients.

“Specifically, there is a need for robust evaluations of interventions aimed at the prevention, early detection, and effective management of psychiatric morbidity, with this important patient-related outcome as a useful end point. As well as improving quality of life, such strategies could assist in the earlier return to work and economic productivity for younger patients and families after stroke,” they write.

References

1. Stroke. 2008; Published online March 27, 2008. [Abstract]

2. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

 NEW YORK (Reuters Health) Mar 24 - MYO-029, a neutralizing antibody to myostatin, appears to be a safe agent for treating muscular dystrophy, the results of a phase I/II trial suggest. [1]

Except for some skin reactions with the highest doses tested, MYO-029 showed good safety and tolerability, the findings indicate. Whether MYO-029 has any clinically meaningful effect, however, remains to be determined.

Aside from corticosteroids, which provide only modest benefit to some patients with muscular dystrophies, there are no treatments that improve muscle strength, according to the report in the Annals of Neurology for March. [1]

Myostatin is an endogenous inhibitor of muscle growth, and therefore could serve as a target for therapies aimed at improving muscle mass and strength. In studies of immunodeficient mice, treatment with MYO-029 has been shown to increase muscle mass by roughly 30% over a 3-month period.

In the current study, a research team led by Dr. Kathryn R. Wagner, from The Johns Hopkins University School of Medicine in Baltimore, assessed the safety of MYO-029 in 116 patients with Becker muscular dystrophy, facioscapulohumeral dystrophy, or limb-girdle muscular dystrophy.

The subjects were randomized to receive the drug at one of four doses (1, 3, 10, or 30 mg/kg) or placebo. The treatments were administered intravenously every 2 weeks for 6 months, with follow-up for a further 3 months.

Cutaneous hypersensitivity was observed with the 10- and 30-mg/kg doses. Otherwise, MYO-029 appeared safe and well tolerated.

No significant improvements in muscle strength or function were noted, but the authors emphasize that the study was not powered to assess efficacy. There was, however, radiographic and histologic evidence that MYO-029 improved muscle size in some patients.

“This trial supports the hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin for clinical studies, and these inhibitors should be evaluated for stimulating muscle growth in muscular dystrophy,” Dr. Wagner’s team concludes.

1. Ann Neurol 2008;63.

2. Dystrophinopathies [full text]

The author: Professor Yasser Metwally

http://yassermetwally.com

March 27, 2008 — Just as having a big belly increases the risk for cardiovascular disease and diabetes, new research shows that central obesity in midlife is also an independent risk factor for dementia — a finding that also applies to individuals who are not overweight.

A large, population-based study from researchers at Kaiser Permanente Division of Research, in Oakland, California, shows that the presence of central obesity in midlife almost triples dementia risk in later life, independent of diabetes, stroke, hypertension, hyperlipidemia, and heart disease.

The longitudinal analysis of 6583 individuals in northern California who had abdominal fat measurements taken in their 40s showed that, 36 years later, those in the highest quintile of abdominal fat had an odds ratio for dementia of 2.72 compared with those without abdominal obesity.

“More than total body weight, it is where you carry your weight — especially in midlife — that elevates dementia risk,” first author Rachel A. said Whitmer, PhD,

The study is published online March 26 in Neurology. [1]

• Belly Fat More Detrimental

Recent research has also shown that midlife obesity, measured by body-mass index (BMI), increases the risk for dementia, Alzheimer’s disease (AD), and neurodegenerative changes.

Previous research by Dr. Whitmer and colleagues looking at the effect of midlife BMI demonstrated that total body weight is a strong predictor of dementia, conferring a 75% increased risk among those with the highest BMI.

It is also well established that central obesity is an independent and more potent risk factor than total body obesity for type 2 diabetes, insulin resistance, coronary heart disease, stroke, and mortality.

However, said Dr. Whitmer, it was not clear whether central obesity confers a similar elevated risk with respect to dementia as it does with cardiovascular disease and diabetes.

The study included individuals from the Kaiser Permanente Medical Care Program of Northern California who participated in voluntary periodic multiphase checkups between 1954 and 1973 when they were 40 to 45 years old.

The collected data included measurements of sagittal abdominal diameter (SAD) as an indicator of central obesity, thigh circumference as a measurement of peripheral obesity, and BMI. Diagnoses of dementia were obtained from medical records an average of 36 years later.

According to Dr. Whitmer, the large sample size allowed researchers to look at the effects of a large belly above and beyond the effects of total weight. As a result, study subjects were categorized by BMI as well as SAD.

• Large Effect

The study revealed that individuals who were both obese and who had a large belly were 3.6 times more likely to develop dementia than those of normal weight and belly size. However, even subjects with a normal BMI but who had a high SAD were 89% more likely to develop dementia.

“I was surprised by the magnitude of our findings. I thought that once we took into account other cardiovascular risk factors, particularly diabetes, the impact of belly fat would have been attenuated. But instead, we found people who were obese and who had a large belly had a hazard ratio of 3.6, which is huge relative to the effect of BMI alone [on dementia risk],” she said.

Of the total study group, 1049 (16%) participants developed dementia. Age-adjusted incidence rates of dementia by quintiles of SAD showed an increase in dementia risk across quintiles, with a steep increase in incidence among those in the fifth quintile.

Fully adjusted multivariate analyses showed that SAD increased dementia risk in a dose-dependent fashion so that individuals in the second quintile were 20% more likely to have dementia, those in the third quintile 49% more likely to have dementia, those in the fourth quintile 67% more likely to have dementia, and those in the fifth quintile 2.72 times more likely to develop dementia vs those in the first quintile of SAD, the authors report.

• The Good News

The study findings, said Dr. Whitmer, suggest there may be something particular about visceral adipose tissue relative to other types of body fat that contributes to poor outcomes, raising the risk for diabetes, stroke, cardiovascular outcomes, and now dementia.

“We know visceral adipose tissue is highly metabolically active and secretes hormones and inflammatory products that play a role in insulin resistance, diabetes, and cardiovascular disease, but at this point we don’t know what they do to the brain,” she said.

She added that some mechanistic research suggests such substances including interleukin 6 and leptin play a role in cognitive function. Leptin has been shown in animal studies to cross the blood-brain barrier and may play a role in neurodegeneration, including contributing to deposition of beta amyloid.

However, she added, more research is needed to elucidate potential mechanisms. In the meantime, clinicians should be aware of waist circumference as a potential risk factor for dementia and have a sense of whether their patients are carrying excess abdominal weight.

The good news in all of this, said Dr. Whitmer, is that “although visceral fat is more active and more toxic, studies have shown that it responds well to diet and exercise and actually responds better than other types of body fat.”

References

1. Neurology. Published online March 26, 2008.

2. Alzheimer disease [Full text]

3. Neuroimaging of dementia [Full text]

4. Rapidly progressive dementias [Full text]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

March 27, 2008 — A large, prospective, population-based study suggests that an impaired sense of smell may be one of the very earliest signs of Parkinson’s disease (PD), preceding motor symptoms by several years.

Investigators at the Veterans Affairs Pacific Islands Health Care System in Honolulu, Hawaii, found that men with the worst degree of olfactory dysfunction had a 5-fold increased risk for the development of PD vs their counterparts with the best sense of smell. They also found that an impaired sense of smell can predate clinical symptoms by at least 4 years, although it was not a strong predictor beyond this period.

According to the study authors, the findings are “unique in that this is the first population-based prospective study to demonstrate that odor identification deficits can predate the development of clinical PD in men by at least 4 years.”

Led by G. Webster Ross, MD, the study is published in the February 2008 issue of the Annals of Neurology.

Olfactory dysfunction is commonly associated with PD and occurs with the same frequency as resting tremor. Evidence from cross-sectional studies indicates that patients frequently have problems with their sense of smell before being diagnosed with PD. However, it is unclear whether olfactory dysfunction may be an early sign of PD in the general population.

To examine this association, investigators recruited 2267 men aged 71 to 95 years who were participants in the Honolulu-Asia Aging Study, a longitudinal study looking at the development of PD and dementia in men of Japanese ancestry.

All subjects underwent olfactory testing with the Brief Smell Identification Test at least once, were free of PD and dementia at the time of testing, and were observed for up to 8 years. During the follow-up period, 35 men were diagnosed with PD.

• 4-Year Threshold

Decreased odor identification was associated with older age, smoking, higher levels of coffee consumption, less frequent bowel movements, lower cognitive function, and excessive daytime sleepiness.

However, even after adjustment for these factors, individuals in the lowest quartile of olfactory function had an odds ratio for PD of 5.2 (95% confidence interval, 1.5 - 25.6) vs their counterparts in the top 2 quartiles, the study authors report.

“One interpretation of this finding is that the relation of olfactory deficits to greater risk for future PD begins to weaken beyond a threshold of approximately 4 years between testing and diagnosis,” they write.

This finding is supported by the fact that the time from olfactory testing to diagnosis was shortest among those with the lowest olfactory scores.

In addition, findings from earlier studies suggest that olfactory impairment begins between 2 and 7 years before diagnosis, and estimates from neuroimaging and pathologic studies suggest that there is a period of approximately 5 to 7 years between the onset of nerve loss in the substantia nigra and diagnosis of the disease.

• Early Screening

The study authors note that although the pathologic process of olfactory dysfunction in PD is not completely understood, neuronal loss and Lewy body formation, thought to be markers of PD, are known to take place in the olfactory structures of patients with the disease.

Previous research suggests that the olfactory structures are one of the first brain regions to be affected by Lewy degeneration, supporting the hypothesis that an impaired sense of smell could be one of the earliest signs of the disease.

Another possible explanation for olfactory deficits in PD, the study authors note, is impaired olfactory neurogenesis. They note that the olfactory bulb consists of 1 of 2 regions in the brain that receive new neurons throughout life. Previous research has shown that dopamine depletion, which occurs in PD, impairs neurogenesis in the olfactory bulb in mice.

However, according to the study authors, it is also possible that olfactory deficits in PD are not entirely linked to pathologic processes in the olfactory structures but may be linked to neurodegeneration in the amygdala.

“Olfactory testing together with screening for other potential early indicators of PD such as constipation or sleep disturbances could provide a simple and relatively economic means of identifying individuals at high risk for development of PD who could participate in trials of medications designed to prevent or slow disease progression,” the study authors write.

“More expensive, but conceivably more specific tests such as transcranial echosonography or dopamine transporter imaging might narrow this at-risk population even further,” they conclude.

The study was supported by the National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke), the Office of Research and Development, Medical Research Service Department of Veterans Affairs, and the US Department of the Army.

• Clinical Context

Olfactory dysfunction is a prominent symptom of PD, and a study by Doty and colleagues, which appeared in the August 1988 issue of Neurology, quantified the olfactory deficit associated with PD. In this study, patients with PD and control subjects underwent a smell identification test as well as an odor detection threshold test. Patients with PD fared worse on both examinations, and the olfactory deficit among these patients was unrelated to other disease symptoms or to the duration of PD. A total of 72% of patients with PD and a smell disorder were unaware of their deficit before testing, and the degree of olfactory deficit associated with PD was similar to that previously demonstrated in patients with Alzheimer’s disease.

Other research has suggested that olfactory dysfunction actually predates clinical PD. The current study examines this issue.

• Study Highlights

  1. The current study focuses on the Honolulu-Asia Aging Study cohort. All subjects were men of Japanese descent who were between the ages of 71 and 95 years at the time of assessment. All participants were free of clinical PD and dementia at baseline.

  2. Olfaction was assessed with 2 examinations with the Brief Smell Identification Test from 1991 to 1993 and 1994 to 1996.

  3. Incident PD was diagnosed by patient self-report, the use of medications for PD, and a clinical examination. The final diagnosis of PD was established by the consensus opinion of at least 2 neurologists.

  4. The main outcome of the study was the effect of olfactory function on the risk for PD. This relationship was adjusted for potential confounders including age, smoking, coffee intake, and cognitive function.

  5. 2267 subjects were included in the current study. The mean age at the beginning of follow-up was 79.7 years.

  6. 35 men in the study cohort were diagnosed with incident PD, and the average time to a diagnosis was 4 years.

  7. Reduced olfaction was associated with older age, a greater number of pack-years of smoking, excessive daytime sleepiness, and reduced cognitive function.

  8. The incidence of PD was 54.5 cases per 10,000 person-years among men in the lowest quartile of olfaction vs 26.6, 8.2, and 8.4 cases among participants in the successively higher quartiles of olfaction.

  9. After adjustment for potential confounders, the relative risk for PD among men in the lowest quartile of olfaction vs those in the highest 2 quartiles was 5.2, and the relative risk among men in the second quartile vs those in the highest 2 quartiles was 3.1.

  10. The increased risk for incident PD was significant for subjects with reduced olfaction during the first, but not during the second, 4 years of follow-up.

  11. A subgroup analysis removing subjects with the lowest cognition scores failed to alter the main result of the study, which was that reduced olfaction increased the risk for incident PD.

  12. A diagnosis of PD also occurred more rapidly among subjects with lower olfaction scores.

• Pearls for Practice

  1. A previous study demonstrated that PD was associated with reduced olfaction, regardless of other disease symptoms or the duration of PD. Most patients with PD and reduced olfaction did not realize that they had a deficit.

  2. The current study demonstrates that reduced olfaction can predict an increased risk for PD in the subsequent 4 years among a cohort of older men.

References

1. Ann Neurol. 2008;63:167-173.

2. The idiopathic parkinson disease [Full text]

3. Parkinson disease [Full text]

4. Management of parkinson disease [Full text]

5. Neuroprotection in parkinson disease [Full text]

6. Parkinson-plus syndromes [Full text]

7. The akinetic-rigid syndromes [Full text]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

March 28, 2008 — A new analysis of data from the Leukoaraiosis and Disability Study (LADIS) shows that the severity of gait and balance problems in the elderly correlates with age-related white-matter changes (ARWMC) seen on magnetic resonance imaging (MRI).

In this cross-sectional analysis, researchers found a “clear, dose-dependent” effect of ARWMC burden on several measures of balance and gait.

“Walking difficulties and falls are major symptoms of people with white-matter changes and a significant cause of illness and death in the elderly,” lead author Hansjoerg Baezner, MD, PhD, from the University of Heidelberg, in Mannheim, Germany, said in a statement from the American Academy of Neurology (AAN).

They did find that physical exercise was associated with better results on gait and balance testing and speculate that exercise may have a protective effect in delaying the transition to disability. “This hypothesis is currently being addressed in our longitudinal study,” the authors write.

Their findings are published in the March 18 issue of Neurology.

• A Major Cause of Morbidity and Mortality

Gait problems and falls are a major symptom of patients with ARWMC and an important cause of morbidity and mortality in the elderly, the authors write. However, increasing age is not enough to explain this relationship, they note.

“A promising theory to explain the progressive decline in motor abilities refers to the complex motor network that guarantees the integrity of central coordination of stance and gait,” they write. “The network may be challenged through a critical amount of lesions in the subcortical regions.”

Motor deficits related to ARWMC present in different ways, they note, including gait apraxia, impaired balance on walking, and increased risk for falls.

In LADIS, coordinated at the department of neurologic and psychiatric sciences at the University of Florence, in Italy, researchers at 11 European centers are looking at the role of ARWMC as an independent determinant of the transition to disability in elderly persons aged 65 to 84 years. The study includes 639 nondisabled individuals who were enrolled prospectively and are being followed for 3 years.

Subjects all had ARWMC on MRI after referral for evaluation of cognitive symptoms, minor stroke, motor symptoms, psychiatric symptoms, or other neurologic disturbances. Each was graded in 3 categories of mild (n=284), moderate (n=197), or severe (n=158) for ARWMC.

Gait and balance were measured using the Short Physical Performance Battery (SPPB) that scores subjects from poor to normal on a scale of 0 to 12, a timed 8-minute walk, and a timed single leg stance.

They report that in this cross-sectional analysis, deficiencies in gait and balance as measured using the SPPB were correlated with the severity of ARWMC, as was walking speed and balance.

Table 1. Results on Short Physical Performance Battery (SPPB), Walking Speed, and Single Leg Stance Time by Severity of Age-Related White-Matter Changes

Individuals who were physically inactive had a higher risk for a pathologic SPPB score, they note, a finding that could be relevant to therapeutic interventions.

“A putative independent intrinsic effect may be explained by the stabilization of the labile neuronal motor network,” they write. “This is a new message because, so far, several small studies have shown a positive effect of physical exercise on selected aspects of mobility in the elderly, but there has been contradictory evidence regarding its influence on gait, balance, and activities of daily living.”

“Mobility is one of the key determinants of independent aging,” they conclude.

Monitoring of age-related white-matter changes may be useful in the early detection of gait and motor compromise that can lead to other health problems.

“Recently, gait abnormalities have been shown to predict non–Alzheimer’s disease dementia, so recognition, early diagnosis, and treatment of this disabling condition may be possible through early detection of walking and balance problems,” Dr. Baezner said in the AAN statement.

The AAN recently issued a new guideline on the detection of those at risk for falls.

References

1. Neurology. 2008;70:935-942. [Abstract]

2. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

February 21, 2008 - Individuals who met standard criteria for the metabolic syndrome had at least a 60% increased age- and sex-adjusted risk of new-onset atrial fibrillation (AF) over four and a half years in a prospective community-based study conducted in Japan [1]. The study also found that the AF risk rose with the number of metabolic-syndrome components a person displayed and that most of the syndrome’s components were individually predictive of AF.

“The metabolic-syndrome has a strong association with stroke, MI, and cardiovascular and all-cause mortality,” observe the authors, led by Dr Hiroshi Watanabe (Vanderbilt University School of Medicine, Nashville, TN), “and the increased incidence of stroke and higher mortality in subjects with the metabolic syndrome can be partially explained by its association with AF.”

The group’s analysis, based on annual health examination data from >28 000 persons in Niigata, Japan, was published by Circulation online February 19, 2008. The cohort excluded persons with a history of AF or atrial flutter and those taking “antihyperlipidemic drugs.”

Their baseline prevalence of metabolic syndrome was 13% using National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) criteria and 16% when the definition was based on American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) guidelines. The two definitions differ primarily in the thresholds signifying impaired glucose tolerance, which are >110 mg/dL and >100 mg/dL, respectively, according to Watanabe et al.

The adjusted risk of AF increased by 10% per year of age and was tripled in men as compared with women (p<0.001 for both increases), so multivariate analyses were adjusted for age and sex. They showed significantly increased hazard ratios for AF by either definition: 1.88 using NCEP-ATP III criteria and 1.61 according to AHA/NHLBI criteria. The increase remained significant with the NCEP-ATP III definition (1.78, p=0.03) even after diabetics and persons receiving antihypertensive therapy were excluded.

All of the component risk factors, save raised triglycerides, were significantly predictive of AF.

Table 1. Age- and sex-adjusted hazard ratio for atrial fibrillation by individual components of metabolic syndrome*

*Defined as a presence of at least three of the following: impaired glucose tolerance, obesity (as gauged by body-mass index in the current analysis), elevated BP, low HDL cholesterol, and elevated triglycerides

“Although the pathogenesis of the metabolic syndrome is not well understood, it is likely that the condition represents a complex interplay between metabolic, genetic, and even environmental factors,” according to the group. As “inflammation and oxidative stress have been proposed as common etiologic factors linking these processes and have likewise been implicated in the pathogenesis of AF,” the increased AF risk in the metabolic syndrome “may be related in part to activation of signaling pathways important in inflammation and oxidative stress.” Those signaling pathways, they propose, might make an attractive therapeutic target for lowering the risk of both atherosclerotic disease and AF.

 References

1. Watanabe H, Tanabe N, Watanabe T, et al. Metabolic syndrome and risk of development of atrial fibrillation. The Niigata Preventive Medicine study. Circulation 2008; DOI:10.1161/CIRCULATIONAHA.107.744466. Available at: http://circ.ahajournals.org.

2. The metabolic syndrome and the ischemic microvascular brain events [Full text]
3. The metabolic syndrome [Full text]
4. Metabolic syndrome linked to silent brain ischemic lesions [Full text]
5. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]
6. Atrial fibrillation and stroke [Full text]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

Miyagi, Japan - A prospective cohort study of more than 40 000 people in Japan has shown that drinking green tea can significantly cut deaths from cardiovascular disease as well as all-cause mortality, particularly in women [1]. There was no beneficial effect of green-tea consumption on cancer mortality, however.

Dr Shinichi Kuriyama (Tohuku University Graduate School of Medicine, Miyagi, Japan) and colleagues report their findings in the September 13, 2006 issue of the Journal of the American Medical Association. Kuriyama said: “I think our study provides strong evidence regarding the benefits of drinking green tea in humans on CVD, but not cancer, with a large sample size.

“The reason for the discrepancy between effects on CVD and on cancer deaths in our study is uncertain. Substantial evidence from in vitro and animal studies indicates that green-tea preparations can inhibit both CVD and carcinogenic processes. However, recent epidemiological studies have indicated that green-tea consumption is associated with reduced cardiovascular risk profiles but have demonstrated almost null data regarding the association between green-tea consumption and cancer at various sites. Our results are almost consistent with those of the recent epidemiologic studies.”

• Green tea has largest effect on stroke

Kuriyama and colleagues explain that almost all Japanese people consume green tea as one of their favorite beverages. They designed their prospective analysis to examine the association between green-tea consumption and mortality due to all causes, CVD, and cancer within a large population-based cohort study of 40 530 people in Miyagi Prefecture in northeastern Japan.

Over 11 years (follow-up rate 86.1%), 4209 participants died, and over seven years (follow-up rate 89.6%), 829 people died of CVD and 1134 died of cancer.

Compared with participants who drank less than one cup of green tea per day, those who consumed five or more cups had a risk of all-cause and CVD mortality that was 16% lower (during 11 years of follow-up) and 26% lower (during seven years of follow-up), respectively.

The inverse association with CVD mortality was stronger than that with all-cause mortality, and among the types of CVD, the strongest inverse association was seen for stroke mortality.

Table 1. Cox proportional hazard ratios among all participants for seven-year CVD mortality by green-tea consumption in Japanese adults

*Multivariate HR adjusted for age; sex; job status; years of education; BMI; physical activity; history of hypertension, diabetes, gastric ulcer; smoking status; alcohol consumption; total energy intake per day; daily consumption of rice, miso, soybean products, total meat, total fish, total dairy, total fruits, and total vegetables; and consumption of oolong tea, black tea, and coffee.

• Green-tea effect on CVD, all-cause mortality stronger in women

The inverse association between green-tea consumption and CVD and all-cause mortality was stronger in women than in men (p=0.08 for interaction with sex). In women, the multivariate hazard ratios of CVD mortality across increasing green-tea consumption categories were 1.00, 0.84, 0.69, and 0.69 respectively (p=0.004 for trend).

“The reason for the discrepancy between men and women for the association of green-tea consumption and risk of all-cause and CVD mortality is uncertain,” say the researchers.

“One possibility is residual confounding by cigarette smoking, [as] men were more likely to smoke, and the inverse associations between green-tea consumption and CVD mortality appeared to be more pronounced in participants who had never smoked. These results suggest that higher rates of smoking may mask the association of green-tea consumption with CVD mortality among men.”

They add that the effect of green tea “appears to be a threshold effect rather than a dose-response relationship, such that persons who consume at least one cup a day may receive some benefit.”

A number of biological mechanisms, including radical scavenging and antioxidant properties, have been proposed for the beneficial effects of green tea, they continue, noting that previous studies have suggested that green tea favorably affects hypertension, LDL-cholesterol levels, and atherosclerosis.

However, “clinical trials are ultimately necessary to confirm the protective effect of green tea on mortality,” they conclude.

References

1. Kuriyama S, Shimazu T, Ohmori K, et al. Green tea consumption and mortality due to cardiovascular disease, cancer and all causes in Japan. The Ohsaki study. JAMA 2006; 296:1255-1265.

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

New Orleans, LA - A new analysis from the Northern Manhattan Study suggests that insulin resistance is associated with an increased risk for a first ischemic stroke and combined vascular events in nondiabetics [1].

Researchers report that insulin resistance, defined in this study as a homeostatic model assessment of insulin sensitivity (HOMA) index of >3, was associated with a more-than-doubled risk for ischemic stroke and a 50% increase in vascular events, including MI, stroke, or vascular death, independent of waist circumference, body mass index (BMI), or other components of the metabolic syndrome.

These findings “again raise the issue that it’s not just diabetes but may be prediabetes or insulin resistance that we need to detect and possibly treat to reduce the risk of stroke and vascular disease,” said senior author Dr Ralph Sacco (University of Miami Miller School of Medicine, FL).

The study was presented here at the International Stroke Conference 2008. First author on the paper was Dr Tatjana Rundek (University of Miami).

• Underlying mechanism

This group previously reported that metabolic syndrome is associated with an increased risk for stroke and vascular events [2]. Insulin resistance is an important underlying mechanism of metabolic syndrome, type 2 diabetes, and cardiovascular disease, the authors write. Insulin resistance may affect up to 40% of healthy subjects, but data linking this prediabetic state and stroke risk are “controversial and limited,” they note.

In this study, Rundek and colleagues used data from the ongoing Northern Manhattan Study to look at this association in 1735 nondiabetic subjects who were free of stroke at baseline. The population’s mean age was 68 years, 63% of subjects were women, and it represented a multiethnic cohort: 61% Hispanic, 19% black, and 19% white.

Serum measures of fasting glucose and fasting insulin were used to determine the HOMA index, with insulin resistance defined as a HOMA index of >3.

They used Cox proportional hazard models to determine the effect of insulin resistance on the risk for first ischemic stroke and on combined vascular events, including MI, stroke, and vascular death, adjusting for demographics and traditional vascular risk factors, as well as waist circumference, BMI, physical activity, and alcohol consumption.

The mean HOMA index in this cohort was 2.76 + 7.42. Of the subjects, 25% met the criteria for insulin resistance, with a HOMA index of >3. Over a mean follow-up of 6.9 years, vascular events occurred in 188 subjects, including 38 fatal or nonfatal ischemic strokes, 74 fatal or nonfatal MIs, and a total of 116 deaths from vascular causes.

They found that a HOMA index of >3 was associated with an increased risk for both first ischemic stroke and combined vascular events. “This was true even after controlling for other vascular risk factors such as waist circumference, body mass index, and other components of the metabolic syndrome,” Sacco said.

Risk for stroke and combined vascular events with HOMA index >3 vs <3

Of this population, 63% was Hispanic, Sacco noted. “We have data that indicate obesity and insulin resistance may be even greater prevalent factors in Hispanics, one of the most rapidly growing demographic groups in the United States.”

They plan to further examine the relationship between insulin resistance and other markers of stroke risk, including carotid disease, clinically silent strokes, and white-matter disease, he said.

References

1. Rundek T, Xu Q, Miallman J, Goldberg RB, et al. Insulin resistance and risk of ischemic stroke among non-diabetic individuals from the Northern Manhattan Study. International Stroke Conference 2008; February 20-22, 2008; New Orleans, LA.

2. Boden-Albala B, Sacco RL, Lee HS, et al. Metabolic syndrome and ischemic stroke risk: Northern Manhattan Study. Stroke 2008; 39:30-35.

3.  Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

4. The metabolic syndrome and the ischemic microvascular brain events [Full text]
5. The metabolic syndrome [Full text]

6. Metabolic syndrome linked to silent brain ischemic lesions [Full text]

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

March 28, 2008 — Parental hypertension is strongly and independently associated with higher blood-pressure levels and the development of hypertension over their offspring’s adult lifespan, a new study has shown [1]. Investigators also showed that the age at which parents develop hypertension is important, with early-onset hypertension in parents conferring a greater risk of developing high blood pressure in their children.

“As previously established, parental hypertension does give people information about their risk of developing high blood pressure,” said lead investigator Dr Nae-Yuh Wang (Johns Hopkins University School of Medicine, Baltimore, MD). “With chronic diseases like heart disease, we’re evaluating people from a young age, and when we do we should be trying to determine the hypertension status of their parents and when they developed high blood pressure.”

The results of the study, published in the March 24, 2008 issue of the Archives of Internal Medicine, fall in line with data observed in other cross-sectional studies showing that the risk of developing high blood pressure is clustered in families. These other trials, said Wang, mostly relied on recall of family history, have had short follow-up periods, and have not distinguished between maternal and paternal hypertension. These studies also did not look at the prognostic value of the parental age of hypertension onset. The purpose of this study, he said, was to examine the association of parental hypertension with blood-pressure changes and hypertension risk from young adulthood onward.

• Study of male medical students from Johns Hopkins

Using data from the Johns Hopkins Precursors Study, designed and initiated in 1947, investigators obtained data on 1160 male students at the Johns Hopkins University School of Medicine. All participants underwent medical examinations and reported their medical history, including blood-pressure measurements, at baseline and every five years after graduation. For more than 50 years, the subjects completed annual questionnaires regarding their blood pressure and the diagnosis of high blood pressure in their parents and themselves.

Compared with participants whose parents did not develop high blood pressure, those with parental hypertension had a higher rate of systolic blood-pressure increases over time — 2.9 mm Hg vs 2.6 mm Hg over 10 years. When subjects were 35 years of age, the adjusted systolic blood-pressure value was 1.9 mm Hg, 1.6 mm Hg, and 3.2 mm Hg higher among those with maternal hypertension only, paternal hypertension only, and hypertension in both parents, respectively.

The investigators report that this higher rate of systolic blood-pressure increase associated with parental hypertension translated into a statistically significant higher incidence of hypertension in the cohort. By age 40, the cumulative incidence of hypertension was 5.3% among those whose parents were hypertensive compared with 1.3% among those whose parents had normal blood pressure.

Subjects with both parents with hypertension or those with one parent who was hypertensive before the age of 55 years were at greater risk of developing hypertension, especially at a younger age. Early-onset hypertension in both parents was associated with a greater-than-sixfold increase in the risk of hypertension at any point in adulthood and a 20-fold higher risk of developing hypertension by age 35, a risk that declined as subjects aged.

Table 1. Hazard ratios (HRs) of incident hypertension associated with parental hypertension

Table 2. HRs (95% CI) of hypertension developing at specific ages associated with early- and late-onset parental hypertension

Wang said that the prevalence of hypertension is estimated to be somewhere between 10% to 15% of US white men aged 30 to 39 years or aged 35 to 44 years, depending on the source of information, and that this demographic might not regularly check their blood pressure. “Parents with early onset of hypertension could be a warning sign for these younger men or their physicians to take preventive measures or other appropriate actions,” he said.

• Clinical Context

Hypertension (HTN) has long been recognized as being clustered in families, with a range of 35% to 65% being attributed to the heritable component of HTN. Blood pressure (BP) concordance within families has been linked to both genetic and environmental factors, with concordance stronger among monozygotic vs dizygotic twins. Clinicians may underestimate the contribution of family history of HTN in HTN risk assessment, and previous studies have not distinguished among risks conferred by maternal vs paternal family history vs both parents having HTN.

This is a longitudinal cohort study of medical students who were observed for up to 54 years to examine the effect of parental HTN on the risk for HTN and age of onset of HTN.

• Study Highlights

  1. The cohort was assembled in 1947 and consisted of white male medical students in the classes of 1948 to 1965 from 1 medical school.

  2. Excluded were women and nonwhite students, those with existing HTN, and those who failed to follow up.

  3. The 1160 students in the study completed a baseline questionnaire on health, family history, and a physical examination including weight, height, and BP measurement.

  4. Incidence of parental HTN was established on the baseline questionnaire and by prospective annual questionnaires after graduation.

  5. During medical school, the students received up to 9 repeated measurements of weight, height, and BP.

  6. After graduation, they completed questionnaires on lifestyle and medical history at least every 5 years.

  7. Self-reported BP was elicited annually by questionnaire, and participants were asked to measure their own BP in the seated position.

  8. The average number of years that BP was reported was 13.

  9. Self-reported BP was found to be accurate in a separate validation study, with a correlation of 0.67 for systolic and 0.56 for diastolic BP.

  10. HTN was defined as a reported single measurement of 160/95 mm Hg, 2 or more measurements of 140/90 mm Hg, or HTN requiring drug therapy.

  11. A committee of 5 internists assigned the diagnosis of HTN.

  12. Median follow-up was 37 years since graduation with yearly response rates of 68% to 78%, with 87% of graduates responding at least once during every 5-year period.

  13. Vital status was determined via family members, obituaries, and the National Death Index.

  14. 23% of the cohort reported having a parent with HTN: 127 only in their father, 117 only in their mother, and 20 in both at baseline.

  15. During follow-up, 583 incident cases of parental HTN occurred.

  16. By the end of follow-up, 60% of the cohort had at least 1 parent with HTN (n = 701).

  17. Men with a positive parental history of HTN had higher mean systolic and diastolic BP.

  18. Parental HTN was not associated with participant body mass index, smoking status, alcohol intake, coffee consumption, or exercise frequency at baseline.

  19. A total of 29,867 BP measurements were reported, which were averaged to yield 15,723 annual mean BP estimates.

  20. Mean systolic and diastolic BP at follow-up were higher in those with parental HTN, and the differences persisted into the ninth decade of life.

  21. Participants with a parental history of HTN had a higher mean increase in systolic BP of 2.9 vs 2.6 mm Hg for 10 years (P = .04).

  22. At age 35 years, the adjusted mean BP values were 1.9, 1.6, and 3.2 mm Hg higher among those who had maternal HTN only, paternal HTN only, and HTN in both parents, respectively.

  23. The corresponding diastolic BP increases were 0.9, 0.6, and 2.4 mm Hg, but these were not statistically significant.

  24. The cohort with parental HTN had a significantly higher incidence of HTN, with HTN developing in 448 men by age 57 years.

  25. The cumulative incidence of HTN was 35.8% at age 65 years and 69.2% at age 81 years for those with parental HTN.

  26. Cumulative incidence rates were 4 times higher at age 40 years in men with a parental history of HTN (5.3%) vs those without such a history (1.3%).

  27. The HR for HTN was 1.6 for maternal HTN, 1.8 for paternal HTN, and 2.7 for both parents having HTN.

  28. Early onset of HTN in parents increased the risk for HTN, with a 7.1-fold increased risk for HTN at age 55 years or older.

  29. There was a 20-fold increased risk for HTN at age 35 years for men with both parents having early onset of HTN.

  30. Adjusted HRs for HTN at age 35 years were 20.4 and 2.9 among men with early onset of HTN in both parents vs early onset of HTN in only 1 parent.

• Pearls for Practice

  1. A positive parental history of HTN is associated with an increased risk for HTN.

  2. The risk for HTN and early-onset HTN is greater in those with a stronger family history of HTN and with parental early onset of HTN.

References

1. Wang NY, Young JH, Meoni LA, et al. Blood pressure change and risk of hypertension associated with parental hypertension. Arch Intern Med. 2008;168:643-648.

2. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]

3. Smoking, hypertension and hemorrhagic stroke Risk [full text]
4. Blood pressure and stroke [Full text]