Deans' stroke musings

Changing stroke rehab and research worldwide now.Time is Brain!Just think of all the trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 493 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It's quite disgusting that this information is not available from every stroke association and doctors group.
My back ground story is here:

Monday, October 31, 2011

Menstrual Blood Cells Display Stem Cell–Like Phenotypic Markers and Exert Neuroprotection Following Transplantation in Experimental Stroke

I guess us guys and older women may have to settle for fat stem cells.

Cell therapy remains an experimental treatment for neurological disorders. A major obstacle in pursuing the clinical application of this therapy is finding the optimal cell type that will allow benefit to a large patient population with minimal complications. A cell type that is a complete match of the transplant recipient appears as an optimal scenario. Here, we report that menstrual blood may be an important source of autologous stem cells. Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog), and when grown in appropriate conditioned media, express neuronal phenotypic markers (Nestin, MAP2). In order to test the therapeutic potential of these cells, we used the in vitro stroke model of oxygen glucose deprivation (OGD) and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood exhibited significantly reduced cell death. Trophic factors, such as VEGF, BDNF, and NT-3, were up-regulated in the media of OGD-exposed cultured menstrual blood-derived stem cells. Transplantation of menstrual blood-derived stem cells, either intracerebrally or intravenously and without immunosuppression, after experimentally induced ischemic stroke in adult rats also significantly reduced behavioral and histological impairments compared to vehicle-infused rats. Menstrual blood-derived cells exemplify a source of “individually tailored” donor cells that completely match the transplant recipient, at least in women. The present neurostructural and behavioral benefits afforded by transplanted menstrual blood-derived cells support their use as a stem cell source for cell therapy in stroke.


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Aliquots derived from the 2 samples of cells, passaged either 6 or 9, and grown for additional 3 passages in culture, were found to behave similarly, with cell yields, number of adherent cells and those expressing neuronal phenotypes, as well as graft survival and functional effects showing near complete resemblance of the 2 cell populations. Thus, the data from these 2 cell populations were collapsed into a single treatment condition. A flow chart of experimental procedures is provided (Fig. 1).

Cultured menstrual blood cells display embryonic stem cell-like features

Immunocytochemical assays of cultured menstrual blood reveal that they express embryonic-like stem cell phenotypic markers (Oct4, SSEA, Nanog) (Fig. 2). Greater than 90% of the cells were positive for these pluripotent markers. They maintained these stemness properties at least up to 9 passages plus the additional 3 culture passages (ie, longest time point the cells were cultured in this study). In addition, their growth rate or proliferative capacity did not change over time. Of note, human ES cells showed the typical specific nuclear staining, but we detected a few cells positive for Oct4 show cytoplasmic labeling, which appears to be the pattern of staining displayed by majority of menstrual blood-derived stem cells. While we do not have a solid explanation for such cytoplasmic labeling, this differential pattern of Oct4 labeling may distinguish ES cells from menstrual blood-derived stem cells. Furthermore, menstrual blood-derived stem cells (75%) were CXCR4-positive, a stem cell chemotaxis marker, also expressed by human ES cells. The cells were plated on a coated 10-cm dish in DMEM/F12 supplemented with ITS, and the medium was changed twice a week throughout the study.

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FIG. 2. Cultured menstrual blood cells display embryonic stem cell-like features. Panels A and B are positive control images taken from human embryonic stem cells expressing the phenotypic markers Oct4 and CXCR4. Immunocytochemical assays of cultured menstrual blood reveal that these cells (75%) were CXCR4-positive, a stem cell chemotaxis marker (Panel C). Furthermore, they express embryonic-like stem cell phenotypic markers Oct4, SSEA, and Nanog as shown in panels D–F, respectively. Greater than 90% of the cells were positive for these pluripotent markers. They maintained these stemness properties at least up to passage 9 plus the additional 3 passages in culture (ie, longest time point the cells were cultured in this study). In addition, their growth rate or proliferative capacity did not change over time. The cells were plated on a coated 10-cm dish in DMEM/F12 supplemented with ITS and medium was changed twice a week throughout the study.

Cultured menstrual blood cells can be steered toward neural lineage

After passage 6 or 9, the cells were transferred to coated dishes in neural induction medium (DMEM/F12 supplemented with N2 and FGF-2) for a week, and retinoic acid was added to the medium over the next 3 weeks. Cells were Nestin-positive, indicative of an early neural lineage commitment, and readily differentiated into intermediate neuronal (30% MAP2-positive, but the mature neuronal marker, NeuN, labeling not detected) and astrocytic phenotype (40% GFAP-positive) upon withdrawal of FGF-2 (Fig. 3). Thus, when grown in appropriate conditioned media, cultured menstrual blood stem cells express neural phenotypic markers (Nestin, MAP2).

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FIG. 3. Cultured menstrual blood cells can be steered toward neural lineage. Morphological changes in cultured menstrual blood cells immediately following thawing (A), after a few hours (B), and prolonged exposure (C) in neural induction medium (DMEM/F12 supplemented with N2 and FGF-2). After passage 6 or 9, the cells were transferred to coated dishes in neural induction medium for a week, and retinoic acid was added to the medium over the next 3 weeks. Cells were Nestin-positive, indicative of an early neural lineage commitment, and readily differentiated into intermediate neuronal (30% MAP2-positive, but the mature neuronal marker, NeuN, labeling not detected) and astrocytic phenotype (40% GFAP-positive) upon withdrawal of FGF-2. Thus, when grown in appropriate conditioned media, cultured menstrual blood stem cells express neural phenotypic markers (Nestin, MAP2).

Co-cultured menstrual blood-derived stem cells protects against in vitro stroke insult

In order to test the therapeutic potential of these cells, we used the in vitro OGD stroke model and found that OGD-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood-derived stem cells exhibited significantly protected against ischemic cell death (Fig. 4). ANOVA revealed significant treatment effects in both Trypan blue exclusion method (F 2,6 = 58.78, P < 0.0001) and MTT assay (F 2,6 = 45.60, P < 0.001) for detecting cell death and cell survival, respectively. Post hoc tests revealed that menstrual blood-derived stem cells (Trypan blue exclusion method and MTT assay, P < 0.0001 vs. controls) or the media collected from cultured menstrual blood-derived stem cells (Trypan blue exclusion method, P < 0.0001 vs. controls; MTT assay, P < 0.001 vs. controls) significantly reduced cell death and improved cell survival of OGD-exposed primary neurons. There were no significant differences in the protective effects afforded by co-culturing with menstrual blood-derived stem cells and exposure to the media collected from cultured menstrual blood-derived stem cells (P > 0.1).

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FIG. 4. Co-cultured menstrual blood-derived stem cells protects against in vitro stroke insult. Cell viability tests using Trypan blue exclusion method and MTT assay revealed that oxygen glucose deprivation (OGD)-exposed primary rat neurons that were co-cultured with menstrual blood-derived stem cells or exposed to the media collected from cultured menstrual blood-derived stem cells exhibited significantly protected against ischemic cell death. There were no significant differences in the protective effects afforded by co-culturing with menstrual blood-derived stem cells and exposure to the media collected from cultured menstrual blood-derived stem cells. Error bars represent standard deviations. Data were generated from 2 triplicates of 2 different menstrual blood-derived stem cell samples. Asterisk corresponds to statistically significant difference between conditioned media or menstrual blood-derived stem cells and control.

Cultured menstrual blood-derived stem cells secrete growth factors

As an approach to reveal a mechanism of action underlying the therapeutic benefits of cultured menstrual blood-derived stem cells, we assayed for growth factors implicated as neuroprotective in stroke models. ELISA data showed elevated levels of trophic factors, such as VEGF, BDNF, and NT-3, in the media of OGD-exposed cultured menstrual blood-derived stem cells (Table 1).

21st century database of traditional Chinese medicine released

So if you really think Neuroaid works you could duplicate the ingredients.

Provided under licence to Tim Tec LLC, a US-based life science company, the 'Chem-TCM' database is the most comprehensive of its kind. Featuring over 12,000 chemicals found in plants used in , the database provides a valuable research tool for the pharmaceutical and biotechnology industries, , and the medical profession (including the complementary health sector).

Part-funded by Innovation China UK (ICUK), the database has been developed through collaboration between researchers in the Institute of Pharmaceutical Science at King's, Dr David Barlow, Dr Thomas Ehrman and Professor Peter Hylands, and the Shanghai Institute of Materia Medica (SIMM).

To create the Chem-TCM database, the King's researchers analysed patterns in the known and predicted biological activities of 12,000 chemicals from over 300 Chinese herbs in relation to their usage in . Their results reveal that many categories in Chinese medicine are translatable into Western terminology.

Dr David Barlow said: 'Traditional Chinese medicine has undergone a remarkable renaissance in recent years. However, the unique language used to describe categories of medicines has hindered effective understanding of one of the most developed and mature systems of alternative medicine in existence.

'With the Chem-TCM database, future researchers will now be better able to understand the chemical basis of remedies that have been in use for thousands of years. This is likely to be of benefit both in the search for and, equally significantly, in understanding how Chinese medicine works.'

Chem-TCM features four major parts: chemical identification, botanical information, predicted activity against Western therapeutic targets, and estimated molecular activity according to traditional Chinese medicine categories.

Dr. Marat Niazoff, CEO of TimTec LLC, said: 'This database is a comprehensive attempt to link Chinese and Western medicine on the molecular level. It is a great contribution to the further study of natural products and their pharmacological potential. The gathers diverse structural material and a wealth of phytochemical information, opening new possibilities for virtual screening in particular.'

Manyi Cristofoli, Director of ICUK, said: 'I am pleased another ICUK-funded proof-of-concept project has now been commercialised in the pharmaceutical industry – this is a very good example of how academia and industry can successfully collaborate for innovation at a truly international level. The partnership with TimTec opens up a new global channel to jointly realise the wide potential in traditional Chinese medicine.'

Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function

A couple of interesting concepts here, NO, nitric oxide needed for synaptic plasticity, useful for neuroplasticity(I think). A suggestion NO is involved in NO-induced neuronal cell death. Hey, more research needed. Should NO be a hyperacute therapy or not?

Sho Kakizawa, Toshiko Yamazawa, Yili Chen, Akihiro Ito, Takashi Murayama, Hideto Oyamada, Nagomi Kurebayashi, Osamu Sato, Masahiko Watanabe, Nozomu Mori, Katsuji Oguchi, Takashi Sakurai, Hiroshi Takeshima, Nobuhito Saito and Masamitsu Iino

Mobilization of intracellular Ca2+ stores regulates a multitude of cellular functions, but the role of intracellular Ca2+ release via the ryanodine receptor (RyR) in the brain remains incompletely understood. We found that nitric oxide (NO) directly activates RyRs, which induce Ca2+ release from intracellular stores of central neurons, and thereby promote prolonged Ca2+ signalling in the brain. Reversible S-nitrosylation of type 1 RyR (RyR1) triggers this Ca2+ release. NO-induced Ca2+ release (NICR) is evoked by type 1 NO synthase-dependent NO production during neural firing, and is essential for cerebellar synaptic plasticity. NO production has also been implicated in pathological conditions including ischaemic brain injury, and our results suggest that NICR is involved in NO-induced neuronal cell death. These findings suggest that NICR via RyR1 plays a regulatory role in the physiological and pathophysiological functions of the brain.

Cerebrovascular protection by various nitric oxide donors in rats after experimental stroke.

So does this mean we should get NO right after the stroke? Who's going to answer that question?
From 2006, so once again it just shows how badly information about stroke is not followed up.


The efficacy of nitric oxide (NO) treatment in ischemic stroke, though well recognized, is yet to be tested in clinic. NO donors used to treat ischemic injury are structurally diverse compounds. We have shown that treatment of S-nitrosoglutathione (GSNO) protects the brain against injury and inflammation in rats after experimental stroke [M. Khan, B. Sekhon, S. Giri, M. Jatana, A. G. Gilg, K. Ayasolla, C. Elango, A. K. Singh, I. Singh, S-Nitrosoglutathione reduces inflammation and protects brain against focal cerebral ischemia in a rat model of experimental stroke, J. Cereb. Blood Flow Metab. 25 (2005) 177-192.]. In this study, we tested structurally different NO donors including GSNO, S-nitroso-N-acetyl-penicillamine (SNAP), sodium nitroprusside (SNP), methylamine hexamethylene methylamine NONOate (MAHMA), propylamine propylamine NONOate (PAPA), 3-morpholinosydnonimine (SIN-1) and compared their neuroprotective efficacy and antioxidant property in rats after ischemia/reperfusion (I/R). GSNO, in addition to neuroprotection, decreased nitrotyrosine formation and lipid peroxidation in blood and increased the ratio of reduced versus oxidized glutathione (GSH/GSSG) in brain as compared to untreated animals. GSNO also prevented the I/R-induced increase in mRNA expression of ICAM-1 and E-Selectin. SNAP and SNP extended limited neuroprotection, reduced nitrotyrosine formation in blood and blocked increase in mRNA expression of ICAM-1 and E-Selectin in brain tissue. PAPA, MAHMA, and SIN-1 neither protected the brain nor reduced oxidative stress. We conclude that neuroprotective action of NO donors in experimental stroke depends on their ability to reduce oxidative stress both in brain and blood.

Translation please!

Random Noise Stimulation Improves Neuroplasticity in Perceptual Learning

Even after reading this 3 times I don't understand, someone needs to tell researchers they need to put their writings into a useful understandable relation to a therapy. Noise here does not refer to sound.

Perceptual learning is considered a manifestation of neural plasticity in the human brain. We investigated brain plasticity mechanisms in a learning task using noninvasive transcranial electrical stimulation (tES). We hypothesized that different types of tES would have varying actions on the nervous system, which would result in different efficacies of neural plasticity modulation. Thus, the principal goal of the present study was to verify the possibility of inducing differential plasticity effects using two tES approaches [i.e., direct current stimulation (tDCS) and random noise stimulation (tRNS)] during the execution of a visual perceptual learning task.


I wish someone would try this out in humans with a protocol.
Objectives: Wnt/ beta-catenin signaling is essential for maintaining endogenous neurogenesis
in the adult brain1and enhancing post-stroke neurogenesis has been shown to be beneficial for
recovery2-4. Having established that Wnt/ beta-catenin signaling is present within one of the two adult neurogenic niches: the subventricular zone, SVZ, we examined the dynamics of the
signaling pathway following transient middle cerebral artery occlusion, MCAO. We also
investigated the effect of upregulating the pathway on the endogenous post-stroke
neurogenesis, by employing a novel Wnt-3a liposomal preparation.
Methods: - Young adult male Axin 2 reporter mice for Wnt/ beta-catenin signaling were
subjected to 25 min MCAO and cohorts of 4 mice were sacrificed at 1 day, 3 days, 7 days and
14 days post-stroke. Immunohistochemistry was employed to visualize the cell types
demonstrating Wnt/ beta-catenin signaling. Optical density values of images taken at each time
point were compared using ImageJ in order to evaluate pathway activation levels.
- Wnt-3a liposomes were freshly made 5 and injected intra-parenchymally at 1, 3, 7 and 14 days
post-stroke in two 1.5 ul boluses at 3mm and 1.5 mm depth (1.2 mm laterally, 0.6 mm anterior
of bregma).
- DAB staining and stereology were employed to quantify the number of Doublecortin, DCX,
positive newborn neurons at 1 month after MCAO.
Results: - Wnt/ beta catenin signaling was evident in GFAP, Nestin and Doublecortin cells
present at the SVZ in both naïve and post-stroke animals, as well as in mature NeuN positive
neurons within the cortex and striatum. In post-MCAO animals it was also present in GFAP
positive astrocytes at the penumbra.
- We observed an oscillation in the upregulation pattern of Wnt/ beta-catenin signaling after
stroke, which we are confirming with larger cohorts.
- Wnt-3a liposomes exhibited a potent ability to activate the Wnt/ beta-catenin pathway both in
vivo (5 fold greater than baseline) and in vitro (comparable to recombinant Wnt-3a protein) and
significantly increased the number of Doublecortin positive newborn neurons (up to 20 fold
compared to PBS alone) when injected at 3 and 7 days post -stroke.
Conclusions: Here we show that the Wnt/ beta-catenin signaling pathway is active within the
adult brain and upregulated following stroke. Activation of the pathway, in a novel liposomemediated way, significantly enhances endogenous neurogenesis post-stroke.

Leptin Induces Neuroprotection Neurogenesis and Angiogenesis after Stroke.

This has got everything, angiogenesis, neurogenesis, next to lesion.


Leptin is a potent AMP kinase (AMPK) inhibitor that is central to cell survival. Hence, we explored the effects of leptin on neurogenesis and angiogenesis after stroke. Neural stem cells (NSC) were grown as neurospheres in culture and treated with vehicle or leptin and neurosphere size and terminal differentiation were then determined. We then explored the effects of leptin on endogenous repair mechanisms in-vivo. Sabra mice underwent photothrombotic stroke, were given vehicle or leptin and newborn cells were labeled with Bromo-deoxy-Uridine. Functional outcome was studied with the neurological severity score for 90 days post stroke and the brains were then evaluated with immunohistochemistry. In a subset of animals the brains were also evaluated for changes in the expression of leptin receptor and AMPK. In-vitro, leptin led to a 2-fold increase in neurosphere size but did not change the differentiation of newborn cells. Following stroke, exogenous leptin led to a 4-fold increase in their number in the cortex abutting the lesion. There was a 1.5-fold increase in the number of newborn neurons and glia in leptin treated animals. Leptin also significantly increased the number of blood vessels in the peri-lesioned cortex. Leptin treated mice had increased expression of leptin receptor and increased phosphorylated AMPK concentration. Animals treated with leptin also had significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis after stroke and leads to increased leptin receptor and pAMPK concentrations. This may explain at least in part the better functional outcome observed in leptin treated animals after stroke.

Wonder what this does to stop the cascade of death?

Canadian Stroke Network Chooses to Deliver Evidence-Based Care to the Bedside

I would be more impressed with this if there was evidence based care for stroke rehab.
The Canadian Stroke Network and are pleased to announce a partnership to deliver improved health care to patients from coast to coast. By using's advanced order set technology, the Canadian Stroke Network will be able to facilitate the delivery of the latest scientific research directly to the patient bedside.
The CSN stroke order sets are detailed, evidence-based checklists that allow doctors, nurses and other health-care professionals to quickly and easily specify appropriate and evidence-based screening activities, diagnostic testing and interventions for patients presenting to hospital with acute stroke or transient ischemic attack. Order sets will be available for acute stroke management in the emergency department, administration of thrombolysis agents, admission to a stroke unit, admission to a rehabilitation unit, and secondary stroke prevention. provides its client hospitals with a comprehensive web-based order set technology that includes:
                 --  A reference library of hundreds of evidence-based order sets,
 developedin partnership with organizations like the Canadian Stroke Network, who
are the experts in evidence-based care for their patients --  Libraries of
hospital-customized order sets that allow hospitals to share and learn from each other         --  Software that allows clinicians to complete order sets using computers             and/or mobile tablet devices         --  Analytics software that lets clinicians view comparative data on their             use of order sets            's client hospitals are part of a network of more than 160 health-care organizations that work directly with peer hospitals, clinicians and specialty medical organizations like the Canadian Stroke Network to share order sets and maintain evidence-based best practices. The adoption of evidence-based order sets has been independently shown to significantly reduce patient length of stay in hospitals, reduce readmission rates to hospital, and improve patient outcomes. is endorsed by the Ontario Hospital Association as a best practice for hospitals.
Dr. Patrice Lindsay, the Canadian Stroke Network's Director of Performance and Standards, said "The winner in this partnership is the stroke patient - whether on Vancouver Island or PEI, they'll have access to the best evidenced-based care. We're very proud to be able to take our research and guidelines to the next level with to improve people's lives."
Dr. Chris O'Connor, President of said, "It's an honour to be working with the Canadian Stroke Network to improve stroke care. Together, we will bridge the gap between research and practice. And everyday, new hospitals are joining us because they understand that we're stronger when we work together."
About the Canadian Stroke Network:
The Canadian Stroke Network ( brings together Canada's leading scientists and clinicians to reduce the physical, social and economic impact of stroke on the lives of individual Canadians and on society as a whole. Headquartered at the University of Ottawa, the Canadian Stroke Network is one of Canada's Networks of Centres of Excellence.

Sunday, October 30, 2011

The Benefits of Lucid Dreaming

I'm sure there is no research showing how this can help stroke patients, but sometimes we have to blaze our own trails. I look at this as another form of mental imagery. Why waste your sleeping hours, you can do therapy while sleeping. Nothing in Canadas' Strokengine on this.
Or you could read Ursala K LeGuin; The Lathe of Heaven
Ok I found a study;
Dreamed Movement Elicits Activation in the Sensorimotor Cortex.


Since the discovery of the close association between rapid eye movement (REM) sleep and dreaming, much effort has been devoted to link physiological signatures of REM sleep to the contents of associated dreams [1-4]. Due to the impossibility of experimentally controlling spontaneous dream activity, however, a direct demonstration of dream contents by neuroimaging methods is lacking. By combining brain imaging with polysomnography and exploiting the state of "lucid dreaming," we show here that a predefined motor task performed during dreaming elicits neuronal activation in the sensorimotor cortex. In lucid dreams, the subject is aware of the dreaming state and capable of performing predefined actions while all standard polysomnographic criteria of REM sleep are fulfilled [5, 6]. Using eye signals as temporal markers, neural activity measured by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) was related to dreamed hand movements during lucid REM sleep. Though preliminary, we provide first evidence that specific contents of REM-associated dreaming can be visualized by neuroimaging.

Lucid dreaming as a learnable skill: A case study
During a 3-yr study, the author recorded a total of 389 lucid dreams and developed a mnemonic technique for the voluntary induction of lucid dreams (MILD). Without using any induction procedure, the S reported less than 1 lucid dream/month. Using autosuggestion resulted in a range of 1–23 lucid dreams/month, with at most 2/night. MILD yielded 18–26 lucid dreams/month, with up to 4/night. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)
The benefits of lucid dreaming are far-reaching
e new skills.

That's not to mention the enormous fun that comes from playing within your own virtual reality dream world and how it relates to your own subconscious mind. Soon you will see it is all interconnected - conscious and unconscious - enabling you to use this playground for profound personal growth and insights.

And then there is the obvious benefit: pure wish fulfillment. Act out your greatest fantasies in full color. You don't need inspiration for that, do you...?

Improve Your Problem Solving Skills

Scientists understand the benefits of lucid dreaming; some have used it to enhance their problem solving skills in extraordinarily creative ways.

Improve Your Problem Solving SkillsTake Friedrich Kekule's discovery of the structure of the benzene molecule; Otto Loewi's experiment on nerve impulses; and Elias Howe's invention of the sewing machine. These dream-inspired inventions highlight the stunning power of the dreaming subconscious mind.

Once you learn the basics of lucid dreaming, you can solve problems on demand - and on a whole new level. That's because you are not limited by your logical conscious brain. Instead, you can solve problems creatively in a 3D environment, or by drawing deeper insights directly from your subconscious mind. Just ask any question to your lucid dream and wait for the answer...

Improve Your Creativity

Conscious dreaming is an exceptionally powerful way to improve your creativity. Painters like Salvador Dali, William Blake and Paul Klee created famous artwork inspired by dreams.

Even musical composers - like Mozart, Beethoven and Wagner - pointed to dreams as the source of their inspiration. In fact, some of the most beautiful music I ever heard took place in my lucid dreams. They reveal our most creative side because of the free-flow of ideas arising from the subconscious mind.

Salvador Dali was Inspired by His DreamsTo improve your creativity in lucid dreams, you can follow two avenues. First, make an announcement in your dream: "show me something amazing!" Your subconscious will respond in unpredictable but often deeply inspiring ways.

Alternatively, set a lucid dream intention. If you are a painter, take a trip to your own lucid dreaming art gallery and see what you find. If you are a musician, play the piano with Chopin and create a complex new arrangement. By encouraging your conscious dream to show you these things, the response will come as if automatically, straight from the dreaming subconscious.

Face Your Fears

Remember I said the benefits of lucid dreaming are far-reaching? This one may push you to your logical limits.

Conscious dreaming allows you to face your fears in a controlled setting. If you are afraid of heights, why not jump out of an airplane?

In the alternate reality of lucid dreams, you can slow down time for a controlled fall, and float gently to the ground. Once you have done this at 10,000 feet you will be surprised how you feel about heights in the waking world.

How does it work? One explanation is that dealing with a worst case scenario in a positive way creates new neural patterns in your subconscious mind. Reinforcing that belief with more experiences that seem real can dissolve the fear altogether. From skydiving to snakes, you can face your fears and reprogram your subconscious reactions, knowing that absolutely no harm can come to you.

Alternatively, why not ask that spider what he represents? He may give you an astonishing response that finally allows you to rationalize your fear.

Improve Your Confidence

Do you lack confidence in the waking world? If so, you can use conscious dreaming to release your inhibitions and be totally free in a realistic dream world.

If you want to improve your public speaking abilities, you can rehearse the event in a lucid dream. Having practiced your speech in a realistic environment, you will find you have more confidence when it comes to making the speech in real life. Remember - practice makes perfect.

Lucid dreams are a playground for experimentation. You can try out any concept imaginable - from business, to sports, to relationships - anything you like. By rehearsing a situation or simply toying with different outcomes, you can improve your confidence in any number of waking scenarios.

Practice New Skills

By the same token, you can practice new skills in lucid dreams. In Exploring The World of Lucid Dreaming by Dr Stephen LaBerge, there is a testimony from a surgeon. Before going to sleep, he would review his surgical cases for the next day. Then he would practice them in precise detail in lucid dreams. He has a solid reputation as a surgeon because of this, being able to refine and polish his techniques and perform procedures much faster than the average surgeon.

The Benefits of Lucid DreamingBy now, you can see how the benefits of lucid dreaming are limitless. Take a look at this website for martial arts training in lucid dreams. It features images and descriptions of its virtual training rooms, so you can go there next time you are lucid. It also explains how the precision muscle movements you make during dream training is ingrained in your brain - just as if you had been training in the real world.

Explore Alternate Realities

The lucid dream world is made up of many alternate realities. Every time you "wake up" in a new dream scene, you will find strange goings on and new landscapes to explore. They are all completely tangible and life-like.

Just like in science fiction, you can teleport to parallel worlds, explore different timelines, visit alien planets and travel to other dimensions. This is a thrilling proposition that enables you to explore the nature of the physical universe, as your vast subconscious mind sees it. You can even induce an out of body experience (OBE) in a lucid dream and explore the so-called astral realm.

Final Thoughts

As you can see, there are many great benefits of lucid dreaming. I'm most thankful for lucid dreaming because it showed me something very special about the nature of the human mind. I realized that we are fully capable of creating a vivid virtual reality, complete with all five senses, inside our heads. If you think lucid dreaming is anything like normal dreams, or daydreams, think again...

I love the sheer freedom created by lucidity; how it enables me to fly high like a bird without fear of falling - or run through solid objects. I can visit anyone and do anything I want. And beyond the novelty of wish fulfillment, it provides me with a direct channel to my subconscious mind, enabling me to heal past fears and anxieties and regard myself in a whole new light. It's mind-blowing stuff.

Like anything worth doing, learning to wake up in dreams is not necessarily easy. But with practice and patience, anyone can do it. In fact, just by discovering the concept you have already planted the seed to have lucid dreams tonight...

A Neuroimaging Step Toward Reading Your Dreams

'Lucid' dreamers are people who claim they are aware that they are dreaming and can deliberately control their actions in dreams. When people dream that they are performing a particular action, a portion of the brain involved in the planning and execution of movement lights up with activity.

This learned skill presents an opportunity for researchers who are studying the neural underpinnings of our dreams and their findings in Current Biology, made by scanning the brains of lucid dreamers while they slept, give us a glimpse into non-waking consciousness and perhaps create a waypoint toward true "dream reading."

The researchers instructed participants to make a series of left and right hand movements separated by a series of eye movements upon entering a lucid dream state while their brains were scanned. Those eye movements served as a signal to the researchers of what was happening in the dream.

Those studies show for the first time that neural activity observed in the brain's sensorimotor cortex can be related to dreamed hand movements.

The discovery suggests that lucid dreaming in combination with neuroimaging and polysomnography (a more common form of sleep monitoring) may allow the transfer of more sophisticated "brain reading" tasks to the dreaming state, the researchers say. In other words, it might eventually be possible to predict dreamed content by analyzing patterns of brain activity.

"The main obstacle in studying specific dream content is that spontaneous dream activity cannot be experimentally controlled, as subjects typically cannot perform predecided mental actions during sleep," study coauthor Michael Czisch explained. "Employing the skill of lucid dreaming can help to overcome these obstacles."

Martin Dresler of the Max Planck Institute of Psychiatry, says it will also be interesting to investigate brain activity at the moment a dreamer becomes lucid. "The lucid dreamer gains insight into a very complex state: sleeping, dreaming, but being consciously aware of the dream state. This may inform us about concepts of consciousness."

Is Medical Exercise Therapy the Missing Link You’ve Been Looking For?

Not sure how applicable this is to stroke rehab but I liked the small increments changes in weight/position.
See the machine at the url.
Originally founded by Oddvar Holten in Norway, Medical Exercise Therapy (MET) aims to provide patients with the most appropriate exercises throughout the entire treatment and healing cycle. To further discuss Medical Exercise Therapy, Nate Kloosterman PT, DPT and Frank Aerts, PT, CMPT of MET Seminars USA joins PT Talker in this week’s podcast.

Aerts started using MET 20 years ago and became familiar with it through training in Europe. The principles of medical exercise therapy are used in most European countries and are slowly gaining acceptance here. The MET system uses pulley systems and weight equipment that work with smaller increments than traditional equipment. The weights can be increased in increments as small as a ¼ pound or in grams. These super sensitive machines allows patients to increase weight in small increments to provide the right resistance to aid in the healing process

Kloosterman feels a true therapeutic exercise component is missing from the physical therapy programs offered in the United States. He believes MET addresses both exercise and function and works as the perfect adjunct to modalities and manual therapy. He would like to see MET as a part of the techniques embraced by physical therapists throughout the country. To learn more about Medical Exercise Therapy, listen to the full podcast now.

Is Physical Therapy a Form of Torture?

This was always discussed among the patients. As seen from the therapists viewpoint.
Physical therapy can be painful. But is it really a form of torture? To discuss this issue in greater detail, we have two special guests joining us in this week’s PT Talker podcast. Adam Mendenhall, PT, of Southern Utah Physical Therapy and Rehabilitation and his patient Jennifer Weaver, Bureau Chief for Spectrum and Daily News. Jennifer is undergoing physical therapy and recently wrote about the pain associated with recovery and therapy.
Her physical therapist, Adam Mendenhall believes many patients have a preconceived notion that physical therapy will be torture. To minimize a patient’s fears, Adam believes physical therapists need to be frank with patients about the recovery process to help them understand that some pain is common with post-op recovery and rehabilitation. Jennifer agrees that patients need to educate themselves about the healing and recovery process. She also strongly recommends following a physical therapist’s directions for exercises to do at home.
Find out if physical therapists are really torturers in disguise and gain a greater patient’s perspective on physical therapy by listening to the full podcast now.

Melodic Intonation Therapy for Aphasia

This was written up in 1973. Singing has a different center than speech.


A new form of language therapy has been used successfully with aphasic patients who had severe, long-term, stable defects and for whom other forms of therapy had failed. One explanation for these results suggests that latent language capacities of the nondominant hemisphere may be stimulated.

This one has 6 pages and explains it much better. At least this even lists a protocol.
Melodic Intonation Therapy
Shared Insights onHow It Is Done andWhy
It Might Help
Andrea Norton, Lauryn Zipse, Sarah Marchina,
and Gottfried Schlaug
Music, Stroke Recovery, and Neuroimaging Laboratory, Beth Israel Deaconess
Medical Center/Harvard Medical School, Boston, Massachusetts, USA
For more than 100 years, clinicians have noted that patients with nonfluent aphasia are
capable of singing words that they cannot speak. Thus, the use of melody and rhythm
has long been recommended for improving aphasic patients’ fluency, but itwas not until
1973 that a music-based treatment [Melodic Intonation Therapy (MIT)] was developed.
Our ongoing investigation of MIT’s efficacy has provided valuable insight into this
therapy’s effect on language recovery. Here we share those observations, our additions
to the protocol that aim to enhanceMIT’s benefit, and the rationale that supports them.
Key words: Melodic Intonation Therapy; nonfluent aphasia; language recovery; brain
plasticity; music therapy

Theories on coronary-myocardial disease puzzle

I assume they would also apply to strokes. Found this at the infarct combat project. Ask your neurologist which one s/he subscribes to.

The ECG Vectorial Theory of Myocardial Infarction, 1958

The ECG Vectorial Theory of Myocardial Infarction, 1958

The ECG Vectorial Theory of Myocardial Infarction, 1958

Explains the ECG Patterns of Right / Left Ventricular Infarction

The Myogenic Theory of Myocardial Infarction, 1972

Main therapy: Cardiac glycosides

The Acidity Theory of Atherosclerosis, 2006

Main therapy: Stress reduction and sympatholytic agents

Eating 3 bananas a day could 'slash stroke risk by 21pc'

I know I posted about this earlier but it is important.
Reading this there seems to be a disconnect. It talks about the potassium reducing blood pressure and also reducing chances of a blood clot. Since these are two completely different causes of stroke it seems counter-intuitive that both can be accomplished with the same item. This is an observational study which doesn't really prove anything. But I do wonder if potassium pills would do the same thing.

British and Italian researchers have found that eating three bananas cuts the risk of a stroke.

They said that having one banana for breakfast, one for lunch and one in the evening would provide enough potassium to reduce the chances of suffering a blood clot on the brain by around 21 per cent.

The findings suggest that thousands of strokes could be prevented by the consumption of other potassium-rich foods such as spinach, nuts, milk, fish and lentils, reports the Daily Mail.

Although some previous studies have suggested bananas could be important for controlling Blood Pressure and preventing strokes, results have not always been consistent.

In the latest research, scientists analysed data from eleven different studies - dating back to the mid-Sixties - and pooled the results to get an overall outcome.

They found a daily potassium intake of around 1,600 milligrammes, less than half the UK recommended daily amount for an adult of 3,500mg, was enough to lower stroke risk by more than a fifth.

The average banana contains around 500 milligrammes of potassium, which helps to lower Blood Pressure and controls the balance of fluids in the body.

Too little potassium can lead to an irregular heartbeat, irritability, nausea and diarrhoea.

Researchers from the University of Warwick and the University of Naples said potassium intake in most countries is well below the recommended daily amount.

But if consumers ate more potassium-rich foods and also reduced their salt intake, the annual global death toll from strokes could be cut by more than a million a year.

The study has been published in the Journal of the American College of Cardiology.

stroke rehab bowling

This is the third stroke group I have gone to, this one has people in it who are living rather than waiting for someone to fix them. They organize a bowling get-together every Friday afternoon. I did a 116 and 99 this week with 2 strikes and 5 spares. My walk up is not very smooth but I get to the line with some arm speed. Fun is had by all. We even have a wheelchair bound guy stand at the line and have someone hand him the ball and he successfully bowls.

Testing Treatments - Better Research for better Healthcare

A very good handbook that all our stroke researchers should be following. 226 pages worth
The table of contents.
1 New – but is it better? 1
2 Hoped-for effects that don’t materialize 13
3 More is not necessarily better 21
4 Earlier is not necessarily better 31
5 Dealing with uncertainty about the effects of treatments 50
6 Fair tests of treatments 64
7 Taking account of the play of chance 85
8 Assessing all the relevant, reliable evidence 92
9 Regulating tests of treatments: help or hindrance? 105
10 Research – good, bad, and unnecessary 115
11 Getting the right research done is everybody’s business 130
12 So what makes for better healthcare? 143
13 Research for the right reasons: blueprint for a better future 160

Reply to Irish Health on Urgent action needed on stroke services

My reply to this article was rejected.
article here:
My reply, I thought it was damn good.
If you think about it you could get more for your money if you start researching hyperacute therapies that stop the cascade of neuronal death. Some have only been tested in mice and rats so needed are Phase II and III trials. Literally dozens of these possibilities. Every neurologist should be able to point to the studies I quoted from. Try


"The death of neurons in the brain can be triggered by an imbalance of oxygen - known as oxidative damage, or where cells are incorrectly instructed to die by a neurotransmitter - a process known as excitotoxicity. KCC2 protects against both.

Mannan Binding Lectin-Associated Serine Protease-2 (MASP-2),
By binding with a molecule known as PAR polymer, Iduna prevents the movement of cell-death-inducing factor (AIF) into a cell’s nucleus.
It’s not just a delay of death, but real protection that lasts for about 72 hours.”
Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death
Several years ago, scientists realized that the same enzyme that gives bats more blood for their bite may also help stroke victims by breaking down blood clots. Dubbed Draculin, this blood-clot-bashing drug has now entered a phase 2 study:
extends that window up to 9 hours

One compound, called CNB-001, which was derived from curcumin,

Irish coffee injection(caffeinol),
The experimental drug, called caffeinol, has the potency of two cups of strong coffee and a small shot of alcohol. When injected into rats within three hours of an artificially stimulated stroke, brain damage was cut by up to 80 per cent.

xenon gas,

Earlier preclinical work by the team showed that xenon was effective as a neuroprotectant, stopping processes present during strokes or brain and spinal cord injuries that would damage nerve cells. They found that xenon was capable of blocking the effects of a particular type of glutamate receptor, the same receptor implicated in the pathway that leads to nerve cell death.
Sigma-1 receptors,
Professor Tadeusz Wieloch and his colleagues have found a way to activate a protein in the brain, the sigma-1 receptor, which plays an important role in the brain’s recovery during the critical period after the injury.
We then injected the rats with a specific substance that activated the sigma-1 receptor and found that the rats regained their function more quickly than the untreated animals”, explains Professor Wieloch.
Of course he doesn't say what the injected substance is but it has to be published somewhere.

Alpha-B-crystalline: this is the name of the substance, which reduces the inflammatory response. Naturally present in the lens of the eye (the transparent lens located behind the iris), this protein would significantly reduce the size of the consecutive stroke brain. 12 hours after the stroke.
alpha-B-crystallin, acts as a brake on the immune system, lowering levels of inflammatory molecules whose actions are responsible for substantial brain damage above and beyond that caused by the initial oxygen deprivation of a stroke.
When systemically administered 24 hours after stroke,perlecan, domain V,was well tolerated, reached infarct and peri-infarct brain vasculature, and restored stroke-affected motor function to baseline pre-stroke levels
the genetic activation of the nucleic acid protein Caspase-3 – a member of the cysteine-aspartic acid protease (caspase) family – is a major factor in loss of neuronal tissue and associated apoptosis (programmed cell death).
Carbon nanotubes (CNTs) have been used as a delivery vehicle
CNTs to deliver small interfering RNAs – nucleic acids which block gene expression – to stop production of this enzyme.
"The destiny of neurons in a damaged brain depends on a tiny equilibrium between pro-survival and pro-death signals. We wanted to know what KCC2 was signalling for - was it killing neurons or protecting them after an injury? Our study has found that KCC2 actually rescues the damaged cells."
But when they artificially increased the levels of KCC2 (by stimulating its expression using gene therapy), they found the damaged cells were protected from further damage, and death.

CDB3 peptide spares neurons from death following traumatic brain injury following stroke and accidents. injection within 2 hours.

Timing Control for Paired Plasticity

A patent on this, still don't know what it does.
Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.

a video on the Micro Transponder stroke therapy.
This blog at least gives a description.

Friday, October 28, 2011

World stroke awareness Day -Oct. 29

My take on this is working for the good rather than the perfect. The perfect would be to have everyone lead a healthly lifestyle and not get strokes. Well that won't occur, so lets start figuring out how to reduce the disability caused by stroke.
Or you can believe in the postings by stroke asssociations:
Every six seconds, regardless of age or gender – someone somewhere will die from stroke.
Time is Brain
and give your the FAST, Face, ARMS, Speech, Time mnemonic
Mine has nothing to do with those, Contact your stroke associations and researchers and demand to know what they are doing to stop the cascade of neuronal death. We can probably save more people from disability if we figure out how to stop this than from any Stroke awareness days.

Sorry about the stridency but no one is looking at the big picture

More evidence for lowering LDL to below 70 post 2

I had to post another on this topic because the responses to this are very interesting to read.
you can register for free at this site. I don't think anyone knows what to do about cholesterol.
Eddie Vos

Mortality benefit: MEGA or MIRCO
Thank you Dr. Blanchet for your input. The study of the 3rd URL in posting #34 was done to include the new [open label] MEGA. It covered ~34,000 on-statin female years [~58,000 for men] and concludes "statin therapy reduced the risk of CHD events in men without prior cardiovascular disease, but not in women. Statins did not reduce the risk of total mortality both in men and women.
Comment: we now have 2 studies where mortality benefit derives from the chance finding of fewer cancer deaths, JUPITER [gender not known] and MEGA [in women]. May I refer to a wonderful editorial by John Spertus [CircOutcomes 2011; Medline 21586724] where he highlights ISIS-2 where post MI benefit was found in all groups except in Geminis and Libras. Chance findings [cancer deaths, not incidence] DO happen with statin.
Conflict: I'm a Gemini with a 1/2 semester on statistics, have thrown several statistics books but still own 2 and do a p value in ~3 minutes.
Author's disclosure (Oct 19, 2011)
I have no relevant disclosures to make in connection with this topic.

# 38 of 39
October 22, 2011 10:26 (EDT)
Wiliam Blanchet
All cause mortality vs cardiac mortality
Although there are several studies showing a value with reduction in cardiac events as well as all cause mortality with statin use, Voss is correct in that there is precious little DATA regarding improvement in cardiovascular mortality when the only difference between treatment and control groups is the use of a statin.
Sadly, the message from the east coast experts is often that the only treatment of proven value is statin and that doing anything other than using statin is unnecessary and of no value. I think we need to hear what Ed Voss is saying. If all we do is prescribe a statin and think our job is done, we are horribly mistaken.
I believe that statins help. Statins are often part of the combination of medicine, supplements and lifestyle modifications that I have applied and which have resulted in dramatic reduction of heart attacks and strokes in my practice.
Author's disclosure (Oct 13, 2011)
I use CAC and carotid ultrasound to determine who needs therapy and stability of plaque burden to determine adequacy of treatment.

# 37 of 39
October 22, 2011 09:01 (EDT)
Eddie Vos
A MEGA difference [pravastatin 5 years]
For those not familiar with that study, full text is here:
... 4 cardiovascular deaths per female group and all-cause mortality in men reached a P value of 0.46 and women 10 times lower i.e. 0.046, mainly from less cancer.
Author's disclosure (Oct 19, 2011)
I have no relevant disclosures to make in connection with this topic.

# 36 of 39
October 22, 2011 03:05 (EDT)
D Hackam
...or perhaps not so incidentally, MEGA did show a significant reduction in all cause mortality among women (HR 0.59, p=0.046). How convenient that you did not mention this.
Circulation. 2008;117:494-502.
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 35 of 39
October 22, 2011 02:59 (EDT)
D Hackam
again, you misquote the literature (not surprising)
From the JUPITER paper in Circulation by Samia et al:
"The HR for all-cause death was similarly reduced for women (HR, 0.77; 95% CI, 0.55 to 1.06) and men (HR, 0.82; 95% CI, 0.66 to 1.03). Although this reduction did not reach statistical significance in either sex separately, it was significant when combined (P=0.02). The 5-year number needed to treat to prevent 1 primary end point was calculated to be 36 in women, 22 in men, and 25 when combined."
You lack basic knowledge of statistics. JUPITER was not powered to study all-cause mortality, either overall, or in women alone. It was powered for its primary endpoint (which it met with success; sorry!). What is most impressive is that a statin could reduce mortality in primary prevention with a median follow-up of 1.9 years, and do so across genders (men: 18% relative risk reduction; women: 23% relative risk reduction; combined AND statistically significant - 20% relative risk reduction).
However, it's not that surprising when you consider mortality was also reduced in ASCOT, HPS, 4S, LIPID, SAGE, WOSCOPS, CTT-1, CTT-2, CTT-DM, fatal stroke in SPARCL, CV mortality in A-to-Z, etc. This is clearly a class effect of statins, with better reduction of nonfatal cardiovascular endpoints with more potent statins dosed at higher doses (e.g. TNT, PROVE-IT, SAGE). This is my last post on this thread, as continuing debate presupposes rational arguments on both sides (which do not exist in this case - read your AHA or CCS guidelines, please).
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 34 of 39
October 22, 2011 10:05 (EDT)
Eddie Vos
Mortality: statins ineffective in women, and in most men
Statin mortality benefit: there is none in women :
3 meta analysis [not 'proportional' but absolute] Relative Risks RR = 1.00 RR = 1.00 RR = 0.96
JUPITER: only benefit in women: fewer revascualarizations
wOscops: no women **)
LIPID women: 4500 on statin P-Y vs ditto placebo: mortality P=0.35, "Events" p=0.42
4S: 3 more dead women on statin
ASCOT: mortality not reported, 2 MORE "events" in women
HPS: female mortality not significant.
CTT's female mortality not reported; "proportional" reductions based on the assumption that greater LDL reductions equate to fewer deaths, an assumption invalidated by J-LIT [majority women] where patient outcomes after about 250,000 P-Y of treatment showed SIGNIFICANTLY more deaths the greater the TC and LDL reductions.
ASCOT did NOT report a significant mortality benefit which was confirmed by SPARCL [atorva vs placebo] with NS more deaths on atorva, and by the ~14,246 49 in-house studies [C Newman, Pfizer Global AJC 2006;97:61-67; placebo vs 2 doses atorva] with P=0.03 for more deaths on atorva [degrees of freedom not considered].
**) wOscops selected 1 in 24 screened ~55 year old males; 32,216 P-Y follow-up, vascular mortality p = 0.033 [1.6 vs 2.3%], TOTAL mortality >0.05. 78% current or former smokers. Greatest "event" reduction in middle quintile of delta -LDL, again contradicting the fundamental CTT premise.
In the few studies reporting [male] mortality benefit, this effect appears after about 1.5 years and disappears ~2 to ~3 years later.
Studies that proving no mortality benefit are aplenty: EXCEL, TexCAPS, ALLHAT, other.
Therefore and at best, the NNT for mortality for men is fleeting and gynormous, for women non existent.
Author's disclosure (Oct 19, 2011)
I have no relevant disclosures to make in connection with this topic.

# 33 of 39
October 21, 2011 10:07 (EDT)
Wiliam Blanchet
Another study demonstrating lack of correlation between treatment LDL and MI
Raggi et al. Arteriosclerosis, Thrombosis, and Vascular Biology 2004;24:1272
495 asymptomatic patients with asymptomatic coronary artery disease based on EBT calcium imaging placed on Lipitor. Serial EBT scans were performed. Endpoint of MI was found in 41 subjects.
Average LDL among subjects with MI = 118 mg/dl
Average LDL among subjects without MI = 122mg/dl
Annualized CAC progression among subject with MI = 42%
Annualized CAC progression among subjects without MI= 17%
Risk of MI among subjects with CAC progression > 15% was 17.4 times greater than among those with CAC progression <15%.
Another study showing the lack of correlation between LDL levels and MI. Another study validating the use of serial CAC in determining adequacy of coronary prevention.
Author's disclosure (Oct 13, 2011)
I use CAC and carotid ultrasound to determine who needs therapy and stability of plaque burden to determine adequacy of treatment.

# 32 of 39
October 20, 2011 09:38 (EDT)
D Hackam
missed another
JUPITER - mortality reduced - rosuvastatin vs placebo
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 31 of 39
October 19, 2011 10:31 (EDT)
D Hackam
oops, missed one
WESCOPS - reduced mortality on pravastatin 40 vs placebo
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 30 of 39
October 19, 2011 10:30 (EDT)
D Hackam
reduced mortality
SAGE - reduced mortality on lipitor 80 vs prava 40
LIPID - reduced mortality on prava 40 vs placebo
HPS - reduced mortality on simva 40 vs placebo
ASCOT - reduced mortality on atorva 10 vs placebo
4S - reduced mortality on simva 20 vs placebo
SPARCL - reduced stroke mortality on atorva 80 vs placebo
CTT-1 - reduced mortality
CTT-DM - reduced mortality
CTT-2 - reduced mortality
I haven't even included the trials demonstrating reduced coronary or cardiovascular mortality (such as A-to-Z).
Perhaps patients will harm themselves by stopping their statins and starting supplements such as vitamin E and vitamin C for "cardioprotection". This will increase their risk of hemorrhagic stroke, heart failure and prostate cancer, as demonstrated in HOPE, PHS and the very large prostate prevention trial published a few weeks ago in JAMA.
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 29 of 39
October 19, 2011 10:08 (EDT)
Eddie Vos
What would Dr. Blanchet say ?
The operative word in posting 28 has to be "event", not mortality. It is puzzling that top dose Lipitor or the "dear Canadian doctor" dose 40 mg Crestor should be compounded by fibrate when only one's BMI is over 27.
Some caveats, individual hoped for endpoints with NNTs and more precise patient types come into the picture. Asian patients, for example, have been suggested to take minimal doses of Crestor and NONE of these drugs lowers mortality in anyone [ex. TNT].
Author's disclosure (Oct 19, 2011)
I have no relevant disclosures to make in connection with this topic.

# 28 of 39
October 16, 2011 01:34 (EDT)
D Hackam
treat to plaque regression not target LDL
Plaque regression and stabilization predicts a much lower long-term risk of cv events than plaque progression - by any method: IMT, TPA, MRI, IVUS, CAC, etc. This has been amply demonstrated in prognosis studies. It's one possible titration endpoint.
If you don't have or don't wish to follow vascular disease subclinically then I would suggest adopting the goal doses used in large RCT's like TNT, PROVE-IT, SAGE, etc. 80 mg of lipitor or its equivalent 40 mg of crestor. Add fibrate if TG>200 or HDL<40 in men or <50 in women or BMI>27.
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 27 of 39
October 16, 2011 11:14 (EDT)
In Post MI patients do not check Lipids but Give Statins
Looking at the host of benefits, it appears that statins at any level of LDL Continue to offer further CV benefits
Author's disclosure (Oct 16, 2011)
I have no relevant disclosures to make in connection with this topic.

# 26 of 39
October 15, 2011 10:56 (EDT)
Wiliam Blanchet
HDL trend
I realize you don't know me well enough to know that when I referred to the HDL trend, I was joking as there was a trend toward higher HDL in the group with progression by angiography.
Author's disclosure (Oct 13, 2011)
I use CAC and carotid ultrasound to determine who needs therapy and stability of plaque burden to determine adequacy of treatment.

# 25 of 39
October 15, 2011 10:50 (EDT)
Wiliam Blanchet
LDL levels do not correlate with disease control vs progression
Comparison of coronary artery calcium progression by electron beam computed tomography and angiographically defined progression
Tomomitsu Tani, et al . The American Journal of Cardiology
Volume 91 • Number 7 • April 1, 2003
43 subjects followed for 1 to 5 years with EBCT calcium score and quantitative angiogram within two weeks of each other at baseline and end of study period.
They were evaluated for risk parameters between subjects with angiographically progressive plaque vs angiographically stable plaque.
Progressive plaque Stable Plaque
LDL 116 126
HDL 53 47
Hypertension 50% 64%
Smoker 30% 15%
EBCT Progression 117% 16%
Although a small study, there was absolutely no correlation between LDL and angiographic plaque progression. HDL had a trend however it did not come close to statistical significance.
The only factor that correlated with angiographic plaque progression was the annualized change in EBCT calcium score with 117% progression in EBCT in the angiographically progressive group vs 16% annualized increase in the angiographically stable group p= .002.
This "old" article laid the foundation for more recent studies that demonstrate that progression of calcified plaque is indeed the best predictor of vascular outcomes as well as all cause mortality.
Author's disclosure (Oct 13, 2011)
I use CAC and carotid ultrasound to determine who needs therapy and stability of plaque burden to determine adequacy of treatment.

# 24 of 39
October 13, 2011 05:06 (EDT)
To prove causal association, Experimental Design is necessary and required
ASSOCIATION BETWEEN 2 VARIABLES PROVEN BY EPIDEMIOLOGICAL STUDIES WILL NOT ESTABLISH CAUSAL RELATIONSHIP UNLESS THE STUDY IS AN EXPERIMENTAL DESIGN. Analysis of data of AMI Registry is not an experimental design but a clinical outcome study. Meta-analysis of findings (e.g., RR or HR) of published studies will create false conclusions, as the definition of each numerator and denominator differs greatly among the studies in comparison. Experimental design consists of taking an observation at each one of all possible combinations of factors, ‘nCr’ = n!/r!(n - r)!, which can be built for the different levels of the factors. This is called treatment combination. In Factorial Experiment, the trials are conducted for ‘n’ factors, each at 2 levels, and the trials are performed for 2n times, one at each combination of levels of factors. If the number of factors to be investigated is huge, it will be too hard for the investigator to carry out all possible combination under uniform conditions. In such cases, grouping within a factorial design, which is called “Block Factorial Design”, is to be chosen as an appropriate method of study to lessen the experimental error induced by “the confounding effect” of variables. Sometimes, a study will require a large number of tests, which will create problem in analysis. In such cases, “Fractional Factorial Design”, an experiment based upon carefully chosen subset of combinations of factors, is to be chosen as the method of choice. These are examples of various experimental designs among others.
To my knowledge, the studies that have been done so far in the field of AMI management with “the statin dosage” as a factor, have never used the EXPERIMENTAL DESIGNS that I have described. Therefore, FDA should not make any recommendation to approve or not approve a treatment regimen as a result of the findings based upon the EPIDEMIOLOGICAL STUDIES, OBSERVATIONAL STUDIES, OR CLINICAL OUTCOME STUDIES that are incapable of taking into consideration all the factors that have attributed to MI and its related co-morbidities in a treatment process.
Alternative procedure to experimental design, even though not at all perfect, in establishing cause-effect relationship in a longitudinal study (which does not include registry data analysis) is to carry out multiple regression analysis on all variables that are PATHOLOGICALLY causing each outcome of interest. To be able to fit in the variables for such analysis, data on variables should be gathered using carefully designed data collection form and applying meticulously thought-out definition on each method of measurement, and Structural Equation Modeling (SEM) is to be created. All immediate clinical, laboratory, and other test outcomes, after the exposure of each factor, are to be monitored at regular interval that will be decided upon by the attending physician and must be measured in accord with the definition of measurement. However, SEM cannot be created in all longitudinal studies unless required criteria are met and measurement method for each exposure factor is flexible enough to be changeable in accord with the set definitions.
Previous finding results based on association between 2 variables will not place that factor in the etiological status, as far as MEDICINE is concerned. It may be true for sociology and psychology. All medical professionals have known what factor would cause which pathology, and these professionals do not rely on results of epidmiological study when designing a clinical trial that will prove the pathogenic factor of any outcome. Pathology starts with the birth of Medicine, this field has already established etiological factors for any available conditions that are in existent.
Author's disclosure (Oct 5, 2011)
I have no relevant disclosures to make in connection with this topic.

# 23 of 39
October 13, 2011 04:34 (EDT)
William Feeman, Jr
Dr Blanchet
In my article on the prediction of plaque stabilization/regression on serial angiograms using a risk factor graph (available on my website under the Published Articles--the specific article was in the Journal of Cardiovascular Risk in 2000), I showed quite the opposite. I used the Cholesterol Retention Fraction (CRF, or [LDL-HDL]/LDL) to demonstrate just that. Since very low HDL levels will almost always result in a high CRF, I also showed that LDL levels could predict angiographic stabilization/regression of plaque.
Author's disclosure (Oct 5, 2011)
I have no relevant disclosures to make in connection with this topic.

# 22 of 39

October 13, 2011 12:07 (EDT)
CJ McConnell
Calcified plaques,.. ...are actually "flecks" of,.. [Ca/Pi] complexes,..
...are actually "flecks" of Phosphorus/Ca++ complexes,..
Reduce the serum phosphorous as clsoe to 3 as possible & calcification halts in the majority of cases,... reversing it,.. well, that is another matter. Phosphorous drives ectopic "calcification" ["phosphication"],.. predominantly. This correlates well with long-term development in early CVD & even mortality. Heavy intake of phosphorus, especially inorganic [food additives] in studies following 'normal' healthy adolescents into adult-hood. The calcification is somewhat opportunistic as per damaged endothelium & lipid deposition,.. In the presence of long-term low-level phosphate-intoxification, pericytes slowly transform into 1st chondrocytes & much later osteocytes. the 'positive' CAC is merely a final confirmation of a decades-long process. Sometimes Monksberg's medial but more commonly, "basic" endothelial calcification. many studies infer monitoring slow increase in pulse-wave velocity & a more practical approach, pulse-pressure > 50. The arterial stiffening occurs long before the calcification,.. 'ectopic vascular "bone" formation',.. Most of this data is from the Nephrology journals, but the long term effects data [re: phosphorus] is from "healthy adolescent populations,.. not CKD. The mechanisms are essentially the same,...
Author's disclosure (Oct 10, 2011)
I have no relevant disclosures to make in connection with this topic.

# 21 of 39
October 13, 2011 11:56 (EDT)
CJ McConnell
RE: Dr. Blanchet,.. great point,..
LDL is ana amalgam & ApoB even more so,..
they all respond variably to statins,.. 1 barely moving & Lp(a) not at al,.. more often Lp(a) increases on 2 statins, in particular [see the J Clin Lipidology roundtable on Lp(a) before inserting foot in mouth]. The above list only includes the individual Apo-B fractions that are known to be found within the atherosclerotic plaque. I always ask,.."What do you mean when you say LDL ??" A Friedwald derived LDL ? ,.. direct-LDL ? 'Pure' LDL ? Statins lower most known vascualr inflammatory markers,.. niacin even more so. Who has studied high vs. low dose to see if the inflammation correlates better with improved RRR vs. merely LDL ?
Author's disclosure (Oct 10, 2011)
I have no relevant disclosures to make in connection with this topic.

# 20 of 39
October 13, 2011 12:59 (EDT)
Wiliam Blanchet
LDL levels and calcified plaque progression
In studies of plaque progression, there is no correlation between LDL levels and any of the following; calcified plaque progression, soft plaque progression by quantitative angiography and hard coronary events.
Author's disclosure (Oct 13, 2011)
I use CAC and carotid ultrasound to determine who needs therapy and stability of plaque burden to determine adequacy of treatment.

# 19 of 39
October 12, 2011 02:48 (EDT)
Rochelle Gellatly
Lipid theory doubts
Thanks for those who responded to me, however, I still cannot see the trials that randomize patients to particular "target LDLs". The meta-analysis quoted for me looks at intensive statin therapy vs. moderate dosing - not targeting lipid levels. These lipid levels that we have created many beautiful grafts about are observations from randomized trials, not randomized data themselves. Freeman - I will review your editorial seeking answers, thanks!
Author's disclosure (Oct 6, 2011)
I have no relevant disclosures to make in connection with this topic.

# 18 of 39
October 10, 2011 10:56 (EDT)
CJ McConnell
RRR vs. ARR, 25% is NOT 25%,....
These 'lower-is-better' studies are not shifting the "burden" of ARR all that much,.. still far > 50% on therapy have an event,.. if the low-dose statin arm sees a RRR of 35% & high-dose RRR is 40% the ARR very small indeed,... ARR changes of 1%-4% do NOT dramatically reduce the burden,..
Author's disclosure (Oct 10, 2011)
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# 17 of 39
October 9, 2011 02:07 (EDT)
William Feeman, Jr
Dr Sinclair
As I pointed out in my publication in the Journal of Cardiovascular Risk in 1999 on cigarette smoking and ATD (you can see the article on my website), cigarette smoking can induce ATD events even when lipid levels are ideal. If a cigarette smoker with an LDL of 70 mg/dl had an AMI, I would not place him on a statin long term--but given th vasodilatory effects of statins, I might give a statin to him to get through the acute event, which is probably due to a thrombosis induced by cigarette smoking. I can think of one such patient who did quite well without statins and has had no more AMI's since he quit smoking. (Once that happened, his lipids became abnormal and I did then put him on a statin.)
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# 16 of 39
October 8, 2011 06:38 (EDT)
The results, per se, should not be used as a proponent for further reduction in LDL
The study is a simple analysis of the registry database for patients who had AMI with baseline LDL-C <70, and who survived at discharge from the hospital. It is done through analysis of Korean Acute MI Registry for the period, November 2005 and December 2007. Then HR is calculated using c X r table: primary endpoints vs. statin given or not given at discharge (statin group n = 607; nonstatin group n = 447). It is clear that medical records review was not done, and the investigators, therefore, have no way of finding out all the co-morbidities (those that I mentioned in post #3) that were co-existed in the patients with the intended endpoint. Variables that were entered in the registry are not comprehensive enough to cover those I have mentioned. Unless medical record review is done and data relevant to the outcomes (factors that are contributory to the primary endpoint) are abstracted by a physician/ pathologist, the findings depicted in the table is not acceptable as a reflection of a true situation. There are many other medicines that have not been given at discharge, particularly anti-arrhythmic agents, without which or with inappropriate dosage range of which (even if they were provided), patients will have the above outcomes, the primary endpoint searched by the study. Another important factor to be considered is whether any of these patients has to go through cardiac arrest that needed ACLS immediately before the primary outcome of interest. If so, the deaths or recurrent MI associated with these patients are surely not the result of what the study is trying to prove for, the statin. I am also sure the investigators have not analyzed death certificates, where one is going to find the followings:
· Final disease or condition resulting in death (Immediate cause of death)
· Sequentially list conditions, if any, leading to the cause stated.
· Underlying cause (disease or injury that initiated the events resulting in deaths) is to be stated last.
These vital record data are not certified by epidemiologists, but by PHYSICIANs, and it is always true. All counties in US have Vital Records Departments that keep the aggregated data of deaths. I am sure the investigators would not have reviewed the DCs of the persons who have died.
I do not accept the findings presented by the study that will call for further reduction in cholesterol level than what we have done so far.
It is unethical for the FDA to approve aggressive reduction of cholesterol in United States in favor of cardiac patient management and at the expense of other normal physiological functions (as a result of low cholesterol) leading to many pathologies that will become unavoidable.
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# 15 of 39
October 8, 2011 02:58 (EDT)
James J. King
Where the full profile
In this millennium: Discussing benefits of lowering LDL > 70 mg/dl will requires a more complete lipid profile, like VAP.
HDL2 is large and protective, HDL3 not so much. Lp(a) and IDL are atherogenic, without these measurement discussing LDL has little meaning. A Vitamin D (25 OH) level is also required.
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# 14 of 39
October 8, 2011 11:59 (EDT)
William Feeman, Jr
Global Risk
Dr Zozaya: I published on this about 11 years ago. If LDL is below 80 mg/dl (based on the indirect measurement of HDL, or 70 mg/dl based on the direct measurement of HDL), then HDL is immaterial to ATD (atherothrombotic disease) risk. It is not uncommon for HDL levels to fall when LDL levels fall. If you visit my website, you can see the article in Journal of Cardiovascular Risk in 2000.
Dr Janket: I use dyslipidemia (based on the balance between LDL and HDL), cigarette smoking, and hypertension. Details can be found on my website, or in my Guest Editorial in the current issue of The Lipid Spin.
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# 13 of 39
October 8, 2011 11:33 (EDT)
Sok-Ja Janket
epidemiologic view
I wrote a commentary regarding the multifactor- adjusted randomized trial results are applied in a univariate decision making. Reviewers some were my epidemiology prof. ( I could tell by the way they write.) said, I was mistaken.
Let me ask all of you 1). in randomized trial, two compared groups are even regarding the risk factor distribution (by randomization). Usually, the table 1 shows no risk factors are sig. different. So, multifactors are (adjusted by randomization) to be equal between the interv. group and placebo group. So for example, a trial showed statin gives CV benefit and when LDL lowered to below 70. I wrote using JUPITER and CRP level but I replaced this with LDL 70 now to make a point.
Now, at the clinicians office, like yours, you determine to Rx. statin judging from LDL level only. Is this scientifically correct? I have supported Framingham risk assessment algorithm because CVD is multifactorial and risk assessment should be done as such. So, I wrote multivariate analyses were applied as a univariate in clincial application. Was I wrong?
Was it William Feeman, Jr who mentioned about hypertension, smoking, and obesity in the risk assessment in other blog?
If you wish to decide by LDL alone, you must first assess how this LDL level performs as a clinical decision maker. Otherwise, you are plunking $ in the drain. In your mind, you are helping your patients, but it may just be an illusion. I said this about CRP and a certain group got very angry at me. Now I am saying the same to LDL.
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# 12 of 39
October 8, 2011 12:21 (EDT)
Alberto Zozaya
a question
sometimes I see that when a get LDL´s level lower than 70 I also see that HDL gets lower levels too. Could anyone of you explains me this phenomena.Thanks!.Besides I´m also intrigued about the fact that even nobody disagree about the beneficial effects of statins on atherosclerosis there are little and confusing evidence about their harmful effects.
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# 11 of 39
October 7, 2011 06:23 (EDT)
He who knows probability model can tell firmly that the above results have the confounding effects
Trials that do not take into consideration all factors that are attributing to the outcomes, "Death/recurrent MI/target vessel revascularization/CABG; Cardiac death; Coronary revascularization” is imperfect. No interpretation should be made from that table as there are confounding effects clearly seen from that table. The associations that have been proven by previous trials on the effect of low statin on the above outcomes are merely spurious associations, because all subjects that were included to those studies have factors other than low stain, which are already proven as significantly contributed to the above outcomes. Causal Path Analysis have never been done on the extent of contribution by each factor to these outcomes.
Besides, there is no study that have proven the association between low statin dose with the above outcomes in NORMAL PATIENT POPULATION, who are having normal cholesterol diet. PERIOD. There are a lot of people who are taking high cholesterol diet without taking any statin and yet they do not get the above outcomes.
Anyone who has a chance to look at Atomic Force Micrograph of a cell membrane knows that the effect of aggressive lowering of cholesterol has devastating effect on membrane transport that acts as a key to medical treatment of cardiac patients with drugs utilizing membrane channels.
MIND YOU THAT CELL MEMBRANE IS LIKE A SANDWICH THAT IS COMPOSED OF PHOSPHOLIPID BILAYERS WITH CHOLESTEROL MOLECULES IN BETWEEN. "THE RAFT PHOSPHOLIPIDS HAVE A RICHER SUPPLY OF CHOLESTEROL THAN SURROUNDING REGIONS, AND ALONG WITH ATTACHED MEMBRANE CHANNEL PROTEINS, FORM RATHER RIGID FLOATING PLATFORMS IN THE SURFACE OF MEMBRANE. RAFTS ARE ESSENTIAL IN CONTROLLING CELL MEMBRANE FUNCTIONS." With lower supply of cholesterol, cell membrane is destabilized and its supporting function to the membrane channel proteins will be weakened jeopardizing cellular transport mechanism. Besides, once the time is reached for cell membrane turnover, "the continuous process of loss and replacement of a constituent (as a cell or tissue) of a living system", it will be hard to find the cholesterol necessary for the newer building of cell membrane of a particular cell, because 'Statin' has done enough to deplete the supply of cholesterol for such turnover.
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# 10 of 39
October 7, 2011 12:50 (EDT)
Daniel Earley
Vegetarian Chimps?
Chimpanzees may not eat as much meat as humans, but I hate to break the news to LaRosa that they do, in fact, eat meat. Not only are insects "meat" (even with considerable fat content), but in fact chimpanzees have even been documented to organize hunts. Moreover, a primary evolutionary difference between humans and other primates is homo-erectus' and homo-sapiens' significant leap in hunting capability. If LaRosa's hypothesis were true, humans would have experienced a corresponding decrease in lifespan rather than the increase that occurred. For an evolutionary touchstone, it's far better to look at modern hunter-gatherer tribes than chimpanzees.
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# 9 of 39
October 7, 2011 12:37 (EDT)
Don Phillips
Incomplete Story
Without seeing the rate of hospitalizations from all causes and the rate of deaths due to all causes for the patient categories, the results don't have much meaning.
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# 8 of 39
October 7, 2011 12:09 (EDT)
Vince miraglia
Would anyone here believe the same results would occur with lets say Ezetimebe.? Also the overall all cause mortality data was not provided does anyone have that data.
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# 7 of 39
October 6, 2011 08:05 (EDT)
D Hackam
The above meta-analysis compares intensive to less intensive statins. It would be nice to have a meta-analysis of intensive vs placebo. Since moderate vs placebo definitively gives mortality reductions, intensive vs placebo should be around 1.5-2x that of moderate vs placebo using an imputed placebo analysis.
A recent 40 year old patient of mine who had an ACS and DESx2 was put on atorvastatin 20 mg/d and several months later had a de novo plaque rupture and progression of atherosclerosis in that bed. The initial recommendation on first ACS was to uptitrate the statin - it was never done. This is a non-smoker totally normoglycemic (doc'd by OGTT) normotensive to hypotensive patient. Had he been on atorvastatin 80 mg/d his risk of a further ACS would have been reduced by about 30% (MIRACL trial) and stroke by 50% (again MIRACL) versus placebo. Fortunately he is now on 80 mg/d.
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# 6 of 39
October 6, 2011 08:00 (EDT)
D Hackam
The relevant trials are TNT, PROVE-IT-TIMI-22, SEARCH, IDEAL, SAGE, Post-CABG, A-to-Z Z Phase. The risk reduction for "more statin" vs "less statin" in the 5 biggest trials is about 25%. The most definitive meta-analysis of all these trials (about 10 of them) was published by Ed Mills in Eur Heart J. I quote its abstract below.
Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients
Edward J. Mills1,2,*, Christopher O'Regan3, Oghenowede Eyawo1, Ping Wu1, Fergal Mills1, Otavio Berwanger4 and Matthias Briel2,5
+ Author Affiliations
1Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada V5Z 4B4 K1n6X1
2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
3Department of Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
4Research Institute HCor (Instituto de Ensino e Pesquisa - Hospital do Coracao, HCor) São Paulo, SP-Brazil
5Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland
*Corresponding author. Tel: +1 7783178530, Fax: +1 7783178530, Email:
Received July 29, 2010.
Revision received December 2, 2010.
Accepted January 7, 2011.
Aims Statin therapy is associated with important benefits for patients at risk of, and with, established cardiovascular disease. There is widespread interest in whether intensive dosing of statins yields larger treatment effects. We aimed to determine if intensive dosing is clinically important using a meta-analysis of randomized clinical trials (RCTs).
Methods We conducted comprehensive searches of electronic databases from inception to December 2010. We included any RCT evaluating a larger dose with a clinically common dose. Two reviewers independently extracted data, in duplicate. We performed random-effects meta-analysis and a trial sequential analysis.
Results We identified 10 RCTs enrolling a total of 41 778 participants. Trials followed patients for mean of 2.5 years. We did not find statistically significant effects on all-cause mortality [relative risk (RR) 0.92, 95% confidence interval (CI), 0.83–1.03, P = 0.14, I2 = 38%] or cardiovascular disease (CVD) deaths (RR 0.89, 95% CI, 0.78–1.01, P = 0.07, I2 = 34%). When we pooled the composite endpoint of coronary heart disease (CHD) death plus non-fatal myocardial infarction (MI), we found a significant protective effect of intensive statin dosing (RR 0.90, 95% CI, 0.84–0.96, P ≤ 0.0001, I2 = 0%). We also found a significant effect on non-fatal MIs (RR 0.82, 95% CI, 0.76–0.89, P ≤ 0.0001, I2 = 0%) and a significant reduction in the composite of fatal and non-fatal strokes (excluding transient ischaemic attacks) reported in 10 RCTs (RR 0.86, 95% CI, 0.77–0.96, P = 0.006, I2 = 0%). A subgroup analysis of three trials examining acute coronary syndrome patients found significant effects on all-cause (RR 0.75, 95% CI, 0.61–0.91, P = 0.005, I2 = 0%) and CVD mortality (RR 0.74, 95% CI, 0.59–0.94, P = 0.013, I2 = 0%) with intensive dosing. Applying an analysis of optimal information size on the primary analysis, we found that the evidence for CHD death plus non-fatal MIs is conclusive. The evidence for CVD deaths alone is not yet conclusive.
Conclusions Available evidence suggests that intensive statin therapy reduces the risk of non-fatal events and may have a role in reducing mortality.
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# 5 of 39
October 6, 2011 03:24 (EDT)
William Feeman, Jr
Please read my Guest Editorial in this issue of The Lipid Spin.
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# 4 of 39
October 6, 2011 12:44 (EDT)
Rochelle Gellatly
Lost in translation
Could someone please show me the trial that randomises patients to specific LDL targets? As far as I am aware this data is all observational?
Please help this new clinician understand what all the fuss is about. If you have an event, give them statin, right?
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# 3 of 39
October 5, 2011 04:13 (EDT)
To what extent is attributed by not taking statin in the above outcomes?
Why are you so sure that the events, “Death/ recurrent MI/target vessel revascularization/ CABG; Cardiac death; Coronary revascularization” are the result of not taking statin or lower dose of statin? Have you statistically proven the significant association between lower dose of statin and the above events in normal patients? The table that you have depicted merely reflects the outcomes of ratios based on calculation of risks on the cardiac events and the statin usage. It has not taken into account other variables that can significantly attribute to the above cardiac events. Stratification is needed by the co-administering drugs, dosage of each drug that has been given, co-morbidities, age, ECG findings, presence of specific arrhythmia, the event that has occurred in the patient or that was performed by the patient immediately prior to the above outcomes, and the operative report on previous coronary revascularization procedure or CABG.
As far as HR is concerned, it is based on probability model: i.e., HR = odds = P/(1 – P); P = HR/(1 + HR). You are going to get correct ratio only if there is no overlapping of events. Draw a Venn diagram and fit in all variables that are contributing the 3 outcomes. Nobody can assure you which factor contributes how much in the occurrence of the outcomes of interest. Causal path analysis is needed.
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# 2 of 39
October 5, 2011 12:43 (EDT)
Don Kelsey
Poor correlation.
I wouldn't get too excited about these results. Notice that the 95% confidence intervals are very wide, e.g. from 0.23 to 0.93 for cardiac death, which means there is a lot of scatter in the data and there is a reasonable probability that the relative risk is reduced by perhaps only 10% or less.
And when you add in the potential side effects from high dose therapy, such as now recognized for simvastatin, pushing the "lower is better" envelop may not really be justified.
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# 1 of 39
October 5, 2011 11:48 (EDT)
William Feeman, Jr
How low to go
Statins have a vasodilating effect, which could help explain the benefit seen here. The way to prove it would be to try another agent to bring LDL equally as low and see if the sazme benefit accrued. Of course, this study has nothing to say about primary prevention.