Wednesday, January 28, 2009

 

schizophrenia

Progression of Brain Volume Changes in Adolescent-Onset Psychosis

Santiago Reig; Carmen Moreno; Dolores Moreno; Maite Burdalo; Joost Janssen; Mara Parellada; Arantzazu Zabala; Manuel Desco; Celso ArangoSchizophr Bull. 2009;35(1):233-243. ©2009 Oxford University Press
Posted 01/21/2009

Abstract and Introduction

Abstract

Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.

Introduction

The study of adolescents with first-episode psychosis is of great interest for understanding the pathogenesis of psychosis because younger patients are less confounded by environmental factors such as substance abuse, disease duration, education years, and treatment effects, thus representing a more homogenous patient group. Brain volume abnormalities have been consistently described early in the course of psychosis. Reduction in whole brain and in gray matter (GM) volume, primarily in the frontal and temporal lobes, and enlargement of the lateral ventricles[1-4] are among the most replicated findings in cross-sectional studies of adult patients with first psychotic episodes compared with healthy controls, in line with those typically described in chronic schizophrenia.[5,6] Moreover, early onset psychosis (EOP, first episode before 18 years of age) has been associated with brain changes similar to those reported in chronic schizophrenia.[7-10]

The nature, timing, and course of these structural abnormalities need to be elucidated in order to understand the pathological processes underlying psychosis, in the context of the neurodevelopmental or the neurodegenerative hypothesis.[11] The essential question concerns whether brain abnormalities observed at an early stage are static or progress with time.

Evidence of progressive brain changes during the initial years of psychosis is still not conclusive. Whereas some follow-up studies of first-episode schizophrenia have found progressive reduction of GM volume in the total brain,[12] frontal,[13] parietal and temporal lobes,[14] and enlargement of the lateral ventricles,[12,15] others have failed to detect such longitudinal changes.[16-19] Greater volume decline has been found at follow-up in first-episode schizophrenia patients compared with chronic patients,[13] suggesting that brain changes are more pronounced during the early stages of the illness. Longitudinal brain changes observed in patients with childhood-onset schizophrenia include greater GM loss and larger increase in ventricular volume than controls.[20-23] GM loss in these patients appears to start in the parietal cortex, subsequently spreading through the temporal, frontal, and prefrontal cortices,[24] and frontal atrophy seems to be progressive during adolescence.[25] On the other hand, the only longitudinal study of adolescent-onset schizophrenia showed no progressive changes over a 2- to 3-year period in the prefrontal GM deficit, and in the ventricular enlargement observed relative to control subjects.[26,27]

Most longitudinal studies of first-episode psychosis comprise both adolescents and adults,[12,14,15,19] making it difficult to disentangle the influence of normal development on findings. Longitudinal studies of early onset schizophrenia (with the exception of James et al[26,27]) have included mostly treatment-resistant patients with a considerable duration of illness at baseline scanning.[20-25]

To avoid these confounding factors and minimize the impact of illness and medication on baseline and follow-up conditions, this longitudinal study followed a cohort of psychotic patients with very recent onset of psychosis (under 6 months), short duration of disease, and short antipsychotic treatment prior to scanning. The study includes a matched comparison group of healthy adolescents to control for age-related changes, and all subjects were followed for the same period of 2 years. The cohort of patients is particularly suited for a longitudinal study because it showed structural changes relative to controls,[10] in line with known changes in adults. Based on previous research, we hypothesized that the pattern of change over time would be different between psychotic patients and control subjects, with the former having greater loss of GM. In exploratory analyses, we also sought to determine if volume changes would be different in patients with schizophrenia compared with patients with other psychotic disorders and to assess the influence of clinical status on brain volumes.


# posted by roodbont @ 10:42 AM 0 comments
 

bloeddruk

Human Studies

Antihypertensive Drugs in People Over 80 Years of Age

It is unclear whether we should treat hypertensive people above the age of 80 years with antihypertensive drugs. This hypertensive subgroup on the one hand is liable to adverse events of drug treatment and may die of many diseases unrelated to hypertension, but on the other hand the absolute cardiovascular risk increases dramatically with higher blood pressure. The HYVET study[1] randomized people above the age of 80 and with sustained systolic blood pressure >160 mmHg to placebo or to indapamid, 1.5 mg/day, to which perindopril, 2-4 mg/day, could be added if the target blood pressure of 150/80 was not reached. In other words, the investigators did not examine initial stages of hypertension, let alone high-normal blood pressure, and did not target so-called normal blood pressure <140/90>

Combining ACE Inhibitors and Angiotensin Receptor Blockers Does Not Help

Inhibition of the renin-angiotensin system by ACE inhibitors and by angiotensin receptor blockers is beneficial in people with hypertension, with vascular disease, in heart failure and in proteinuric nephropathies. The combination of both drugs inhibits the renin system more effectively with some further benefits in people with heart failure and in reducing proteinuria to a greater extent than monotherapy with either drug. Adverse events of the combination in heart failure are worrisome as we have detailed in this comment a year ago. The ONTARGET study enrolled 25 600 people with vascular disease, and compared ramipril 10 mg/day with the combination of telmisartan 80 mg/day plus ramipril 10 mg/day and with telmisartan 80 mg/day over 5 years.[2] Although combination therapy had a greater effect on blood pressure (differential 2.4/ 1.4 mmHg to ramipril), it had no benefits on major cardiovascular outcomes. Renal outcomes were more frequent with combination therapy, including the often used combined endpoint of dialysis plus doubling of serum creatinine, while proteinuria was less with combination therapy.[3] No doubt that we should not use the combination to treat hypertension or to prevent major cardiovascular or renal outcomes in people with vascular disease in general, but how about renal subgroups? ONTARGET included 3000 people with microalbuminuria, almost 1000 individuals with macroalbuminuria including 300 people with macroalbuminuria >1 g/g creatinine. We could not detect in any of those proteinuria-based subgroups a signal of renal benefit. Subgroup analyses are fraught with statistical problems and there are issues of power when going to sub-subgroups such as macroalbuminuria >1 g/g. Until further long-term studies dedicated to major renal outcomes are available, we should base our judgements on the ONTARGET trial. The use of combination therapy to lower proteinuria should be restricted to people with albuminuria in excess of 1 g/g and should be discontinued when there is no antiproteinuric effect or when eGFR decreases substantially. In the end, ONTARGET questions the use of proteinuria as a surrogate marker and suggests that we need hard renal outcomes to accept interventions and medications for our patients. The COOPERATE study is no good argument here because that study should no longer be cited until extremely serious concerns about its conduct and analysis have been dealt with.[4,5]

Should We Screen Asymptomatic People for Carotid Artery Stenosis?

It has been argued that people with hypertension should be screened with carotid duplex ultrasound for an increase in intima-media thickness and for carotid artery stenosis even in the absence of cerebrovascular symptoms. The last guidelines of the European Society of Hypertension also favour such screening. The US Preventive Services Task Force, funded by but independent from the US government, has now issued recommendations not to screen in asymptomatic people. The USPSTF performed a systematic review of the evidence for benefit and harm of the screening.[6] The review is revealing; duplex ultrasound is a reliable technique with a sensitivity and specificity ~90% to detect stenoses of >60-70%. However, only a minority of disabling strokes is due to carotid artery stenosis. In centres of vascular surgery with a low complication rate, high-risk people with high-grade carotid stenosis will have a 5% absolute risk reduction over 5 years for stroke and death combined. This risk reduction must be weighted against the harms of screening, namely the risks of angiography when stenosis is suspected on ultrasound and the complications of unnecessary surgery in people with false-positive screening results. It is also noted that a 60-99% stenosis of the carotid artery in asymptomatic people above age 65 may be found in 1% of the population. No single risk factor or predictive rule is known to reliably predict clinically important carotid artery stenosis. It is, however, clear that the prevalence of such stenosis increases with hypertension, male gender, smoking and known heart disease. Based on these considerations and in the absence of a study comparing stroke as an outcome and screening or no screening as interventions, USPSTF does not recommend screening for carotid artery stenosis in asymptomatic people.

Obesity Is Not a Lack of Discipline

Obesity may be a major cause of hypertension as indicated by epidemiological and interventional studies. Many physicians assume that losing weight is only a matter of discipline. We may be wrong. Everyone interested in the subject should read a controversy[7] that reviews all aspects of that matter. There is impressive evidence that body weight is strongly genetically determined. Body weight in identical twins is closely correlated if they are raised in different families; their body weight is not related to their family if it is not the genetic family. The correlation of body weight is weaker in non-identical twins. Apart from rare monogenetic disorders like Leptin deficiency or Leptin receptor deficiency, obesity is a multigenetic disorder. In addition, epigenetic effects, like body weight and fat intake of the mother during pregnancy, play a role. The question then comes up, why does overweight (BMI 25-30/m2) and obesity (BMI >30/m2) increase in recent years, affecting now far more than 50% of adults? The hypothesis is that obesity genes are susceptibility genes, i.e. genes that cause a disease only in a 'toxic' environment. With the abundant availability of fat food and the sedentary lifestyle, such genes break their way. Such gene-environment interactions can be shown in animal models of genetic obesity and in humans. These interactions also explain why abundance of fat food has little influence on the proportion of lean people, who are genetically immune against weight gain, but has a major influence on the massive increase of morbid obesity in recent decades. Given the strong genetic background, it comes as no surprise that the long-term efficacy of weight control programmes is fraught with failure. The majority of interventional weight control studies ended before 1 year; the mean weight loss was 2-5 kg and could be maintained by a minority only. Similarly, attempts to increase physical activity, which may explain about half of the overweight problem, are usually not maintained whenever a specific programme ends. Small changes in weight admittedly result in a significant decrease in blood pressure that matches antihypertensive drug monotherapy. Whether these changes of blood pressure are maintained for more than 1-2 years is unknown. Maybe research of the few patients that successfully maintain a substantial weight loss (everyone of us knows a handful of those) may teach us more. The sad conclusion is that obesity as a genetically determined disease in modern environment has no cure. What to do in our hypertension clinics? We should inform patients about the effects of diet and exercise on blood pressure with prudent guidance of what they can expect. The strong genetic background should be made clear, and failure of a weight reduction programme, which is the rule, should not be blamed on the patient. In morbid obesity, bariatric surgery is effective over many years and has recently been associated with a reduction in cardiovascular outcomes and death with minor effects on blood pressure.

Subtle Kidney Damage First, Hypertension Later?

The kidneys play a major role in regulating blood pressure, and severe diseases of the kidney are commonly accompanied by hypertension. Whether the kidneys play a role in the genesis of primary hypertension is less clear, but there is evidence that people with primary hypertension have a lower number of glomeruli per kidney. The MESA (Multi Ethnic Study of Atherosclerosis) recruited between 2000 and 2002 adults aged 45-84 in the community to study subclinical cardiovascular disease in 6814 participants.[8] Of these, 2767 did not have hypertension or kidney or cardiovascular disease; microalbuminuria and estimated GFR <60>2 were absent in particular. Over 3 years, 20% developed primary hypertension. Of all parameters, a higher baseline cystatin C serum level was associated with the new development of hypertension; a 15 nmol/l higher cystatin C indicated a 15% increase in risk for the development of hypertension. This relationship was absent for serum creatinine or eGFR calculated on the basis of serum creatinine. If anything, participants with a serum creatinine level of 0.8-1.5 mg/dl had a lower incidence of hypertension than those with a serum creatinine <0.8>[8a] The MESA study provides solid evidence that indeed subtle kidney damage contributes substantially to elevated blood pressure, hence to primary hypertension. Still that does not say that any hypertension is a kidney disease and we do not know why in the first place kidney function was reduced in MESA participants developing hypertension and why blood pressure increased subsequently. Further understanding of the pathophysiology may lead to new treatments or, better, prevention of hypertension.

How to Use ACE Inhibitors and Angiotensin Receptor Blockers with Renal Artery Stenosis?

Many textbooks and package inserts list renal artery stenosis indiscriminately as contraindication for the use of ACE inhibitors or angiotensin receptor blockers (collectively called 'angiotensin inhibition' in this paragraph). There are data, however, suggesting that people with renal artery stenosis may specifically benefit from both types of drugs given the fact that (a) they are more effective in lowering blood pressure in renovascular hypertension than other antihypertensives and (b) they lower cardiovascular risk in people with atherosclerotic vascular disease. The latter condition is highly prevalent in people with renal artery stenosis. Hackam et al.[9] note that trial registries show that there are no randomized trials underway testing angiotensin inhibition in renal artery stenosis. The authors, therefore, performed a longitudinal population-based cohort study to evaluate the impact of angiotensin inhibition on renal and cardiovascular outcomes in all people 65 years of age or older in the province of Ontario, Canada. These people are entitled to free, i.e. tax-financed, health care including drug coverage. Data on hospital admissions, discharge diagnoses and interventions, on drug use, on all physician claims and on vital statistics of these Ontario residents are in central registers and were used for the present manuscript. Between 1995 and 2005, 3570 people were detected with a diagnosis of renal artery stenosis, excluding those that concomitantly were on dialysis. Total years of follow-up were 6959, so the mean follow-up time was 2 years. Angiotensin inhibition was defined as a filled prescription of one of these drugs after 3 months of the initial diagnosis of renal artery stenosis (n = 1877). The two groups, treated and not treated with angiotensin inhibition, were remarkably similar in baseline characteristics; if anything, baseline risk was somewhat higher in those treated with angiotensin inhibition. The annual incidence of a primary event (818 events), defined as death, myocardial infarction or stroke, was high, namely 11.8%, but significantly less in those treated with angiotensin inhibition (25% by unadjusted, 30% by adjusted analyses). The absolute benefit was 3 per 100 patient-years for the primary outcome. The population experienced more cardiovascular than renal events, and the single most frequent event was hospitalization for heart failure, occurring in 8%. Treatment with angiotensin inhibition also significantly reduced mortality by 44% (666 deaths) and chronic dialysis (146 cases) by 38%, but increased the risk of hospital admission for acute renal failure; 36 of those episodes were reversible, 24 unfortunately were not. The authors indicate that they cannot offer any data on follow-up serum creatinine or on severity of renal artery stenosis and its lateralization (uni- or bilateral?). Results were independent of intensity of diagnostic or interventional procedures and of number of visits with family doctors or specialists. The authors caution that other antihypertensive agents should be used first in people with renal artery stenosis and if angiotensin inhibitors are used, renal function should be very frequently controlled. I would come to slightly different conclusions because of the striking benefits of angiotensin inhibition in this study and recommend using angiotensin inhibition in most cases of unilateral renal artery stenosis and to strongly consider its use in bilateral renal artery stenosis if blood pressure is not normalized (which is rather the rule). No doubt that we need careful control of kidney function, especially early after initiation of therapy but also later on because renal artery stenoses tend to become tighter with time.

Nephrol Dial Transplant. 2009;24(1):38-42. ©2009 Oxford University Press


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dementia

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Metabolic Syndrome Linked to Vascular Dementia

Reuters Health Information 2009. © 2009 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.

NEW YORK (Reuters Health) Jan 21 - Individuals with the metabolic syndrome, which is known to increase the risk of cardiovascular disease, may also have an increased risk of vascular dementia, but not Alzheimer's disease.

"If metabolic syndrome were also associated with increased risk of developing dementia, the screening and management of its components might offer avenues for prevention of cardiovascular disease and dementia as well," lead author Dr. Christelle Raffaitin of University Hospital Bordeaux, Pessac, France, and colleagues report in the January issue of Diabetes Care. "However, the association between metabolic syndrome, or its individual components, and dementia has received little attention."

The researchers examined the association between the individual components of metabolic syndrome (hypertension, large waist circumference, high triglycerides, low HDL cholesterol, and elevated fasting glycemia) and the risk of incident dementia and its subtypes (Alzheimer's disease and vascular dementia).

Over the 4-year study, 7087 community-dwelling adults without dementia at baseline completed at least one follow-up examination. The subjects were at least 65 years of age and were recruited from the French Three-City cohort.

The researchers report that 15.8% of the participants had the metabolic syndrome, which increased the risk of incident vascular dementia, but not Alzheimer's disease, independent of sociodemographic characteristics and the apolipoprotein E-epsilon-4 allele.

However, the only component of the metabolic syndrome that was significantly associated with the incidence of all-cause (hazard ratio 1.45; p = 0.02) and vascular (hazard ratio 2.27; p = 0.02) dementia was high triglyceride levels. The association remained significant after adjustment for apoE genotype.

A significant association was also observed between diabetes and all-cause (hazard ratio 1.58; p = 0.03) and vascular (hazard ratio 2.53; p = 0.03) dementia. Impaired fasting glucose was not associated with any type of dementia.

The relationship among high triglycerides, diabetes and vascular dementia "emphasizes the need for detection and treatment of vascular risk factors in older persons in order to prevent the likelihood of clinical dementia," Dr. Raffaitin said in an interview with Reuters Health. "Our next step is to study the associations between cognitive decline -- the stage before dementia -- and metabolic syndrome and its components."

Diabetes Care 2009;32:169-174.


# posted by roodbont @ 9:56 AM 0 comments
 

dementia


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Personality May Influence Dementia Risk


Allison Gandey
Information from Industry
ADHD in Adults: How common is it?
Dr Lenard Adler explores the symptoms and prevalence of ADHD in adults.
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January 19, 2009 — A new study suggests there is a link between a person's outlook and lifestyle and their risk of developing dementia. According to work published in the January 20 issue of Neurology, people who are social, active, and not easily stressed may be less likely to experience mental deterioration later in life.

"The good news is lifestyle factors can be modified, as opposed to genetic factors, which cannot be controlled," lead author Hui-Xin Wang, PhD, from the Karolinska Institute, in Stockholm, Sweden, said in a news release. "But these are early results, so how exactly mental attitude influences risk for dementia is not clear."

The good news is lifestyle factors can be modified, as opposed to genetic factors, which cannot be controlled.

Previous studies have shown that chronic distress can affect parts of the brain, such as the hippocampus, possibly leading to dementia. "But our findings suggest that having a calm and outgoing personality in combination with a socially active lifestyle may decrease the risk of developing dementia even further," Dr. Wang explained.

The population-based cohort study included 506 older people who did not have dementia when first examined. Patients were from the Swedish Kungsholmen Project.

Investigators assessed personality traits using the Eysenck Personality Inventory. The questionnaire determined how often each person regularly participated in leisure or organizational activities and the richness of their social network. Participants were followed for 6 years. During that time, 144 developed dementia, according to Diagnostic and Statistical Manual of Mental Disorders III-R criteria.

The researchers found that people who were not socially active but were calm and relaxed had about a 50% lower risk of developing dementia than people who were isolated and prone to distress. The dementia risk was also about 50% lower for people who were outgoing and calm than for those who were outgoing and prone to distress.

Risk for Dementia

Personality and Lifestyle Hazard Ratio 95% CIl
Low neuroticism in socially inactive or isolated people 0.51 0.27 – 0.96
Low neuroticism and high extraversion 0.51 0.28 – 0.94
Low neuroticism and low extraversion 0.95 0.57 – 1.60
High neuroticism and low extraversion 0.97 0.57 – 1.65

"Clinicians should encourage older people to be sociable, active, optimistic, and calm," Dr. Wang told Medscape Neurology & Neurosurgery. "People should have a rich social network and participate in mental, physical, or social activities."

Dr. Wang added that her group was not surprised by these findings. "People with low neuroticism have a more stable mood and better capacity to handle stressful situations without anxiety. Individuals who score high on extraversion usually have more optimistic outlooks on life in general and may be better equipped to cope with stressful events and are therefore less prone to depression."

For these reasons, Dr. Wang said, the researchers anticipated that the stress-dementia hypotheses might be a factor in this study, and the combination of low neuroticism and high extraversion would lead to less stress and a lower risk for dementia.

These findings have significant public-health and clinical implications because the negative effects of certain personality characteristics on dementia are likely to be stress-related and could be buffered by an active and socially integrated lifestyle.

It is estimated that 1 in 7 Americans 71 years and older has some form of dementia. The number of Americans nearing that age is expected to double by the year 2030.

The researchers have disclosed no relevant financial relationships.

Neurology. 2009;72:253-259.



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# posted by roodbont @ 9:54 AM 0 comments
 

schizophrenia bipolar disease


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Schizophrenia, Bipolar Disorder Share Common Genetic Cause


Caroline Cassels
Information from Industry
ADHD in Adults: How common is it?
Dr Lenard Adler explores the symptoms and prevalence of ADHD in adults.
Watch video presentation

January 21, 2009 — The largest family study of schizophrenia and bipolar disorder ever conducted shows that these 2 disorders share a common genetic cause, a finding that challenges the current view that they are separate and distinct conditions.

The analysis, which included more than 9 million individuals from more than 2 million families over a 30-year period, showed that first-degree relatives of individuals with either schizophrenia (35,985 individuals) or bipolar disorder (40,487) had a significantly increased risk for these disorders.

Investigators at the Karolinksa Institutet, in Stockholm, Sweden, found that full siblings were 9 times more likely than the general population to have schizophrenia and 8 times more likely to have bipolar disorder. Maternal half-siblings were 3.6 times more likely to have schizophrenia and 4.5 times more likely to have bipolar disorder than the general population.

This risk was lower for paternal half-siblings, who were 2.7 times more likely to have schizophrenia and 2.4 times more likely to have bipolar disorder.

"Our results were fairly clear-cut and demonstrated that there was a significant increased risk of both schizophrenia and bipolar disorder among first-degree relatives with either of these diseases," study investigator Christina Hultman, PhD, told Medscape Psychiatry. "There was also evidence from the half-siblings and adoptive relatives that this risk is substantially due to genetic factors vs environmental factors, which allows us to conclude that there is a common genetic variation between these 2 psychotic disorders," Dr. Hultman added.

The study is published in the January 17 issue of the Lancet.


# posted by roodbont @ 9:49 AM 0 comments
 

anticoagulans, warfarin, AF

Discussion

The primary finding of this study is the high prevalence of AF among patients with atherothrombosis, ranging from 11.5% in patients with PAD to 13.7% in patients with CVD. Indeed, the prevalence of AF in patients with symptomatic atherothrombotic disease (CAD, CVD, or PAD) was 11.7%. Even among RFO patients, the prevalence of AF (6.2%) is substantially higher than the estimated prevalence in the general population aged 40 years and older (2.3%) and also in the population aged 65 years and older (5.9%).[4] This higher than expected prevalence of AF among patients with atherothrombosis has clinical implications because atherothrombotic patients usually require chronic antiplatelet therapy and frequently protracted periods of dual antiplatelet therapy after acute coronary syndromes or percutaneous coronary intervention.[17-20] As such, the fact that 12.5% of patients with chronic CAD have AF highlights the magnitude of this problem. Yet, prospective trials have not addressed the optimal management of this subgroup of patients with respect to the combined use of oral anticoagulants and antiplatelet agents. The Atrial Fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE-W) trial, however, showed that antiplatelet therapy alone did not provide adequate protection against the risk of stroke in AF patients, compared with warfarin.[21]

Secondly, the study found that AF was associated with a major increase in CV mortality and morbidity, even after adjustment for age, gender, and risk factors. Although the increase in mortality, risk of stroke, and TIA were anticipated,[1,22-24] it is also striking that unstable angina was more frequent among patients with AF, particularly for patients who were enrolled in REACH because of prior CVD or PAD.

Finally, this study shows the higher incidence of chronic heart failure (requiring hospital admission) and severe bleeding in patients with AF at baseline. Importantly, there were notable differences in the baseline characteristics and risk factor profile of patients with AF compared with non-AF patients, with an older age, a higher prevalence of hypertension, and a larger waist circumference. These differences may contribute to worse CV outcomes for patients with AF.

There is a consensus that the presence of AF is a major risk factor for ischemic stroke.[25] However, marked heterogeneity was reported for the risk of ischemic stroke in AF patients, ranging from <2%>10%, depending on the associated risk factors.[26] The CHADS2 score is a simple and practical method for the risk stratification of future stroke in patients with AF.[15] However, the validity of CHADS2 score in predicting future CV events has not been tested in AF patients with or at high risk of atherothrombosis. Our study demonstrates that the CHADS2 score classification was useful in predicting not only stroke but also CV death in stable outpatients with established or at high risk of atherothrombosis. However, it was not as useful in the prediction of nonfatal MI.

Although there is a consensus that oral anticoagulants offer better protection than antiplatelets against ischemic stroke in patients with AF,[21,25-30] the use of oral anticoagulants in these patients in our study was low even with patients at high risk of stroke--an observation consistent with the findings of previous studies, for example, the US Medicare Cohort Study.[31] The low use of oral anticoagulants in the REACH population is coupled with a markedly high background use of antiplatelet agents in patients with, or at high risk of, atherothrombosis. The increased risk of bleeding associated with using combined therapy,[32] in particular aspirin and clopidogrel,[33] could account for the low use of oral anticoagulants observed. Increased risk of bleeding was also associated with aspirin in combination with oral anticoagulant in AF patients with CAD.[34] Clinicians may favor long-term oral antiplatelet therapy over oral anticoagulant or combined therapy: however, unlike previously published smaller studies,[35] ACTIVE-W[21] have established that oral anticoagulants provide superior protection against stroke compared with antiplatelet therapy, even if the latter combines aspirin and clopidogrel.

There are several limitations to this analysis. Approximately 5% of patients were lost to follow-up and an additional 1,388 patients did not have their AF history documented at baseline; however, there were no significant differences in baseline characteristics between these patient subsets and the rest of the cohort.[13] Data on the classification of AF (paroxysmal, persistent, or chronic), duration of AF, or use of antiarrhythmic agents were not available (although a previous study[36] and a meta-analysis demonstrate that this does not influence the risk of thromboembolic events[37]). The presence of AF in the REACH Registry population was determined by participating physicians and not independently adjudicated. Given the large size of the population studied, some of the differences observed in the baseline characteristics of AF and non-AF patients, for example, blood pressure, may be statistically significant but of little clinical relevance. The REACH Registry is an observational registry, which makes it difficult to clarify the causality link between AF and the increased risk of CV events, as this may be in part be confounded by differences in measured or unmeasured baseline characteristics. However, regardless of whether AF is an independent predictor or simply a correlate of higher baseline risk, the presence of AF in patients with atherothrombosis remains a major marker of increased risk of subsequent serious CV events, including CV mortality. We should also emphasize that our data and observations pertain to AF patients with atherothrombosis and should not be generalized to the universal AF patient population.

In conclusion, in this large, global, and contemporary registry, there is a high prevalence of AF among patients with, or at high risk of, atherothrombosis. These patients have a relatively low frequency of use of oral anticoagulants, although they are at high risk of ischemic stroke, probably due to the widespread use of antiplatelet agents for the treatment of atherothrombosis. The presence of AF at baseline was associated with serious and multiple CV events including a higher rate of all-cause and CV mortality, nonfatal stroke, and a modest increase in the risk of acute coronary events including non-fatal MI and unstable angina. Clearly, atherothrombosis patients with AF are a group at particularly high risk of major adverse cardiac events. Efforts should be devoted to improving the care of these patients, particularly to ensure the appropriate use of oral anticoagulants. There is a need for the optimal antithrombotic therapy among AF patients to be clarified to balance the increased risk of thrombotic events and the increased risk of bleeding associated with combined anticoagulant and antiplatelet therapy.

Section 4 of 4
Reprint Address

Shinya Goto, MD, Department of Medicine, Tokai University School of Medicine, Isehara 2591143, Japan. E-mail: shinichi@is.icc.u-tokai.ac.jp

Am Heart J. 2008;156(5):855-863.e2. ©2008 Mosby, Inc.


# posted by roodbont @ 9:11 AM 0 comments

Saturday, January 24, 2009

 

hart heart gender behandeling

Cardiovascular News


Patient, physician gender influences HF treatment


22 January 2009

MedWire News: Treatment for chronic heart failure (CHF) is influenced by both the patient’s and physician’s gender, according to a study appearing in the European Heart Journal.

The findings indicate that women with CHF are less likely to receive evidence-based treatment than men, in particular being less likely to be prescribed ACE inhibitors and receiving lower doses of beta blockers.

They also demonstrate for the first time that patients receive more comprehensive treatment from female than male physicians overall.

Indeed, female physicians did not treat men and women with CHF differently with regard to use and dosages of evidence-based drugs. And women received the worst treatment from a male physician whereas men were best treated by a female physician.

Lead author Magnus Baumhäkel commented: “The use of evidence-based treatments as described in the latest guidelines has undoubtedly improved the treatment of CHF. But there is still evidence of a gender imbalance in both patients and physicians. From our results it seems fair to say that the gender of the physician plays an important role in adherence to drug treatment recommendations in CHF.”

Baumhäkel, from University Hospital of the Saarland in Homburg/Saar, Germany, and colleagues studied 1857 consecutive patients with CHF who were evaluated in centers in eastern Germany between March and November 2006. Data on their co-morbidities, New York Heart Association classification, current treatment, and vital parameters at baseline, the evidence-based treatments they were then prescribed, and the gender, age, and some professional details of the treating physician were documented.

The use of ACE inhibitors and angiotensin receptor blockers (ARBs) was significantly higher in male than female patients (p=0.021) and recommended doses tended to be higher in male patients (p=0.058), the team reports.

Meanwhile, male patients tended to receive beta blockers more often (p=0.075) and received them at significantly higher doses (p=0.021) than their female counterparts.

Of note, the use of ACE inhibitors or ARBs and beta blockers was significantly lower in female patients treated by a male physician than in males treated by either a male or female physician. And the dose received was highest among male patients treated by a female physician, being significantly higher than that received by female patients treated by a male physician.

Beta blocker use was highest in male patients treated by a female physician compared with other possible combinations. Whereas the dose received was comparable in men treated by physicians of either gender, female patients treated by a male physician received the lowest doses of all possible combinations.

Physician’s gender and the interaction of physician’s with patients’ gender proved to be independent predictors for receipt of a beta blocker in multivariable analysis.

Baumhäkel and co-authors conclude: “Physicians should be aware of this problem in order to avoid bias in the treatment of these patients. Further studies are required to provide a detailed explanation of this phenomenon.”

Eur Heart J 2009; Advance online publication



© Copyright Current Medicine Group Ltd, 2009

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Tuesday, January 20, 2009

 

preterm te vroeg geboren


MDI scores =mental development index

Pre-term omega-3 may boost brain development for girls, not boys

By Stephen Daniells, 16-Jan-2009

Related topics: Omega-3, Research, Nutritional lipids and oils, Cognitive and mental function, Maternal & infant health

Supplements of the omega-3 fatty acid DHA may boost the neurodevelopment of prematurely-born baby girls, but premature boys don’t get the same benefits, says a new study.

Over 600 infants took part in the trial, which involved randomising them to receive either a high or standard dose of DHA (docosahexaenoic acid) from day two to four of life until the infants reached their expected date of delivery. DHA intake continued after this date via the mother’s breast milk or infant formula.

Writing in the new issue of the Journal of the American Medical Association, researchers from the Women’s and Children’s Hospital and Flinders Medical Centre in Adelaide, Australia report that measures of memory, problem solving, early number concepts and language were higher in girls who had received the high dose of DHA.

“The lack of responsiveness of boys to the intervention is puzzling, and the reasons are unclear,” wrote the researchers, led by Maria Makrides.

Infants born prematurely are at a higher risk of developing learning disabilities. The study is potentially important because, according to a study published in the British Medical Journal in 2006, the number of premature births increased by 22 per cent between 1995 and 2004. The study was carried out in Denmark, but similar patterns are reported in other European countries.

Study details

Makrides and her co-workers recruited 657 infants born before 33 weeks’ gestation. The initial supplementation involved receiving either high dose DHA (approximately 1 per cent total fatty acids) or the standard dose (approximately 0.3 per cent total fatty acids). Lactating mothers of infants in the high-DHA group consumed six 500-mg DHA-rich tuna oil capsules per day. If supplementary formula was required, infants were given a high-DHA preterm formula.

Of the 657 infants enrolled, 614 completed the 18-month follow-up.

Using the Bayley Mental Development Index (MDI) to evaluate neurodevelopment, the researchers found that no overall differences were observed between the high-DHA and standard-DHA groups. When the MDI scores among girls and boys were considered, a significant increase in MDI scores was noted for girls fed the high-DHA diet than those fed the standard-DHA diet. No benefits were observed in the boys.

Furthermore, MDI scores among smaller infants (weighing less than 1.27 kg (2.8 lbs) at birth) fed the high-DHA diet were higher than that of infants fed standard-DHA, but this wasn’t statistically significant, said the researchers. MDI scores of infants over 1.27 kg at birth did not differ between groups.

“Infants ranged in gestational age from 23 to 33 weeks and, thus, had a range of nutritional stressors, organ immaturity, and [illnesses]. Despite this, the intervention was sufficiently robust to consistently elicit an improvement in the MDI scores of girls and may point the way for higher-dose interventions in future studies. Given the lack of an alternative therapy for cognitive delay in this group of infants and the apparent safety of the current dose of DHA, further studies are warranted,” concluded the researchers.

Disclosures

The authors stated they have no financial interests in infant formula or nutritional supplements. They do note that some of them are members of scientific advisory boards for companies such as Nestle, Fonterra, Wyeth, and Nutricia.

Source: Journal of the American Medical Association
2009, Volume 301, Issue 2, Pages 175-182
“Neurodevelopmental Outcomes of Preterm Infants Fed High-Dose Docosahexaenoic Acid - A Randomized Controlled Trial”
Authors: M. Makrides, R.A. Gibson, A.J. McPhee, C.T. Collins, P.G. Davis, L.W. Doyle, K. Simmer, P.B. Colditz, S. Morris, L.G. Smithers, K. Willson, P. Ryan


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Friday, January 16, 2009

 

warfarin INR

SUMMARY AND COMMENT

Adjusting Warfarin When INR Isn’t in Therapeutic Range

January 15, 2009 | Allan S. Brett, MD

Data suggest that warfarin dose shouldn’t be changed unless INR is ≤1.7 or ≥3.3 (when the target is 2.0–3.0).

Reviewing: Rose AJ et al. J Thromb Haemost 2009 Jan 7:94


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Saturday, January 10, 2009

 

statins

Publication Logo

Statins May Cause Rare Instances of Eye Muscle Disorders


Information from Industry
Contact lens comfort and stability:
A challenge in patients with astigmatism
Accelerated Stabilization Design (ASD) technology
can provide them with the stability they need.
Read more

By Michelle Rizzo

NEW YORK (Reuters Health) Jan 07 - Results of a study published in the December issue of Ophthalmology suggest that diplopia, ptosis, and ophthalmoplegia are associated with statin therapy at normal doses.

Because of "multiple reports of diplopia and ptosis associated with statin therapy" received at their institution, Drs. F. W. Fraunfelder and Amanda B. Richards, from the Casey Eye Institute, Oregon Health & Science University, Portland, investigated adverse events of this type.

They collected spontaneous reports from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, and the Food and Drug Administration. A total of 256 case reports (143 males, 91 females, and 22 gender unspecified) of diplopia, ptosis, or ophthalmoplegia associated with statins were identified in the databases.

The median age of the patients was 69 years. The dosage varied between the different statin drugs, but the average dose was within the range recommended in the package insert for each medication. The average time to occurrence of the adverse drug reaction was 8 months.

Among the 256 case reports, "62 patients discontinued the statin and the diplopia or ptosis resolved," Dr. Fraunfelder told Reuters Health. "Sixteen case reports indicate that the statin was started again and the diplopia or ptosis reoccurred," he said. "This is positive rechallenge data and very compelling evidence that a real adverse drug reaction occurred with statins."

The side effect is rare, however. "It probably represents a localized myositis in the extraocular muscles just as statins can cause myositis in other skeletal muscles in the body," Dr. Fraunfelder noted. "Cardiologists or primary care doctors who prescribe medications in this class (statins) should be aware of this potential adverse drug reaction and consider stopping the drug if diplopia, ptosis, or ophthalmoplegia occur."

Ophthalmology 2008;115:2282-2285.


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omega-3

Fish oils do not prevent arrhythmia


7 January 2009

MedWire News: Dietary supplementation with fish oils is associated with reduced cardiac related deaths but has no effect on the incidence of arrhythmias, indicate meta-analysis findings published online in the British Medical Journal.

Ross Tsuyuki (University of Alberta, Edmonton, Canada) and colleagues systematically examined the association between fish oil supplementation and arrhythmic events.

The meta-analysis included 12 studies and some 32,779 participants, 92% of whom were involved in two trials: the GISSI Prevenzione trial including 11,324 patients randomized to a mixture of the omega 3 fats eicosapentaeonic acid (EPA) and docosahexaenoic acid (DHA) in a 1.2:1 ratio or placebo; and the Japan EPA Lipid Intervention study (JELIS) which included 18,645 patients with hypercholesterolemia randomized to EPA or placebo.

The GISSI trial in particular sparked interest in the potential antiarrythmic properties of fish oils (specifically n-3 polyunsaturated fatty acids, or omega 3 fats), note the researchers, as the reduction in all-cause mortality and cardiovascular death seen in that trial seemed to be driven by a reduction in sudden cardiac death.

Tsuyuki and co-workers report that in three studies including 1148 patients with ICDs, the risk for appropriate ICD intervention was a nonsignificant 10% lower in those taking fish oil supplement than those on placebo.

And there was a nonsignificant 19% lower odds for sudden cardiac death in six studies, totaling 31,111 patients, that looked at this endpoint.

Meanwhile death from cardiac causes was reduced significantly, by 20%, in individuals taking fish oils compared with those not in eleven studies. All-cause mortality was reduced by a nonsignificant 8% among people taking fish oils in the eleven studies evaluating this endpoint.

The authors note that the results were driven primarily by the GISSI-Prevenzione and JELIS trials.

Further analysis failed to find any evidence for a dose-response relationship between DHA and EPA and death from cardiac causes. “Therefore, an ideal formulation for fish-oil supplementation cannot be determined with the currently available evidence,” the authors write.

Subgroup analysis in patients with coronary heart disease revealed a significant 26% reduction in sudden cardiac death (in four trials) and significant 20% reduction in cardiac deaths (in eight trials) with fish oil compared with placebo.

Eric Brunner (University College London, UK) and Hiroyasu Iso (Osaka University, Japan) noted in a related editorial that there was a 20% reduction in nonfatal coronary endpoints, driven by reduced unstable angina, but no effect on fatal outcomes with fish oil in JELIS.

Although they point out that JELIS may have been underpowered to detect effects on fatal endpoints, they commented: “This evidence challenges the proposition, supported by the dramatic reduction in deaths from cardiac disease in a subgroup analysis of GISSI, that the effect of fish oil is mainly the result of electrical stabilization of the myocardium.”

Br Med J 2009; Advance online publication

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