Tuesday, October 16, 2012

Beta Blockers of No Use in Stable Coronary Artery Disease Patients


From Heartwire

Beta Blockers of No Use in Stable CAD Patients

Lisa Nainggolan

 
 
October 2, 2012 (New York, New York) — New registry data indicate that beta blockers do not appear to be of any benefit in three distinct groups of stable outpatients: those with coronary artery disease (CAD) but no history of MI; those with a remote history of MI (one year or more); and those with coronary risk factors only [1].
Lead author Dr Sripal Bangalore (New York University School of Medicine, NY) told heartwire that the evidence for beta-blocker use has mainly been based on old post-MI trials that antedate modern reperfusion or medical therapy and heart-failure trials. People have extrapolated from these trials and assumed that the drugs are also beneficial in those with CAD and even those with just risk factors for CAD, he says, but it is not known if this is justified. Bangalore and colleagues decided to investigate further; they report their findings in the Journal of the American Medical Association, published online October 2, 2012.
Whether they used beta blockers or not in each of these three distinct patient cohorts, we did not see an association with reduced CV events, even in the prior-MI group.
"What we found was pretty interesting. Whether they used beta blockers or not in each of these three distinct patient cohorts, we did not see an association with reduced CV events, even in the prior-MI group. And for some of the outcomes, being on a beta blocker was associated with worse outcomes; for example, there was an increased risk of the primary composite end point--CV death, nonfatal MI, or nonfatal stroke--in patients with just risk factors but no CAD," he notes.
He says that the answer to how long a patient should continue to take a beta blocker after an acute MI is not really known: "As of now, we don't have enough data to answer this. If a patient after a year [following MI] can no longer tolerate beta blockers for any reason, and they don't have heart failure, the data would suggest there is no harm in stopping. If they do have heart failure, however, I would be more inclined to push them a bit further and say, 'This is a great medication; it saves lives.' "
To this end, he stresses that "it is important to understand what this study is not about. It's definitely not about patients who come in after an acute MI or those who have HF--we know there is plenty of data to suggest that beta blockers are beneficial in HF--and also it's not about patients who are on a beta blocker for any other reason, be that for arrhythmias or migraine prophylaxis."
REACH Registry: Data in Almost 45,000 Patients Show Mostly No Benefit
Bangalore and colleagues analyzed data from the Reduction of Atherothrombosis for Continued Health(REACH) registry of 44 708 participants, 14 043 (31%) of whom had prior MI, 12 012 (27%) had documented CAD but without MI, and 18 653 (42%) had CAD risk factors only.
The primary study outcome was a composite of CV death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure; and there were a number of tertiary outcomes. Overall median follow-up was 44 months.
Researchers found that event rates were not significantly different in patients with vs those without beta-blocker use for any of the outcomes tested, even in the prior-MI cohort (16.9% vs 18.6%; hazard ratio [HR] 0.90, p=0.14).
In the CAD-without-MI group alone, rates of the primary end point were not significantly different among those with vs those without beta-blocker use (12.9% vs 13.6%; HR 0.92, p=0.31). And for the secondary end point in this patient group, outcomes were actually worse among those who used beta blockers compared with those who didn't (OR 1.14, p=0.01); this was also the case for the tertiary outcome of hospitalization (OR 1.17, p=0.01).
The same applied to the cohort with risk factors alone, in which rates of the primary end point were higher among those who used beta blockers than those who didn't (14.2% vs 12.1%; HR 1.18, p=0.02), as were rates of the secondary outcome (22.0% vs 20.2%; OR 1.12, p=0.04), but not the tertiary outcomes of MI and stroke.
Randomized Clinical Trials Needed to Define Subgroups of CAD Patients Who Will Benefit
Bangalore says there is somewhat of a disconnect between what current guidelines recommend--which is broadly in line with what he and his colleagues found--and what doctors on the ground are actually doing.
The most recent American Heart Association guidance on secondary prevention, for example, gave beta blockers only a class IIa recommendation for longer-term therapy and a class IIb recommendation for patients with coronary or other vascular disease, note he and his colleagues. And the latest European Society of Cardiology guidelines recommend long-term beta-blocker therapy only in patients with reduced left ventricular systolic dysfunction (class I), he says.
The message is we do need randomized trials in this era of modern medical and reperfusion therapy, even in patients with prior MI, to actually define who is best for beta-blocker therapy and to identify the optimal duration of treatment.
"Though the guidelines are kind of aligned with what we are showing, in practice that's not true. It's common to see beta blockers being prescribed because of the perception that they are perhaps beneficial. But we should be extra careful in making those extrapolations," he told heartwire .
"There are a lot of patients who have had even a remote MI and who are still on beta blockers. And they are prescribed even for people who have had PCI and CABG but who have not had an MI," he notes. And he adds that this drug class is still widely used for high blood pressure despite the fact that it has been downgraded by many hypertension societies to a fourth-line agent for the treatment of this condition.
"The message is we do need randomized trials in this era of modern medical and reperfusion therapy, even in patients with prior MI, to actually define who is best for beta-blocker therapy and to identify the optimal duration of treatment," he concludes.
Bangalore reported no conflicts of interest. Disclosures for the coauthors are listed in the paper.

Low Vitamin D Linked to Alzheimer's Disease


From Medscape Medical News > Neurology

Low Vitamin D Linked to Alzheimer's Disease

Pauline Anderson
    September 28, 2012 — Yet another study has linked low vitamin D levels with significant health issues — in this case, poor cognition.
    In this latest systematic review of the literature, people with Alzheimer's disease (AD) had lower concentrations of vitamin D than those without AD, and better cognitive test results were linked to higher vitamin D concentrations.
    Overall, the results provide sufficient evidence to warrant further investigation to determine whether a cause-and-effect relationship exists, said lead author Cynthia Balion, PhD, a clinical biochemist and associate professor, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
    "I think we have really good data now to make it clear that people need to do the interventional studies and see whether or not giving vitamin D helps people at higher risk for developing cognitive decline," Dr. Balion toldMedscape Medical News.
    The new review was published in the September 25 issue of Neurology.
    Included Studies
    Dr. Balion and colleagues searched MEDLINE, EMBASE, AMED, PsychINFO, and the Cochrane Central database for English-language studies of adults that measured vitamin D levels and included validated tests (for example, global function, executive function, psychomotor speed, attention, memory, or intelligence) as a measure of cognitive function. They accepted all recognized diagnostic criteria.
    The review encompassed 37 studies, including 21 cross-sectional, 10 case-control, 1 before-after with a comparison group, and 2 prospective cohort studies, as well as 3 randomized, controlled trials (RCTs). The study sample sizes varied from 27 to 17,099 participants.
    Thirty studies included only older participants, generally age 65 years or older, whereas 9 studies included only women and 2, only men. Exclusion criteria varied across studies (and included, for example, nutritional supplements, such as calcium and vitamin D; hormonal treatment; and diseases such as kidney disease, liver disease, and osteoporosis.)
    All studies measured 25-hydroxyvitamin D [25(OH)D] concentrations except for 1 that measured 1,25-dihydroxyvitamin D [1.25(OH)D]; 4 studies measured both. Various vitamin D cut points were classified as deficient or insufficient (<25 nmol/L, ≥25 to 50 nmol/L, <50 nmol/L) or sufficient (≥25 nmol/L, ≥50 nmol/L, ≥50 to <75 nmol/L, >75 nmol/L).
    In 14 studies, the cognition outcome included the diagnosis of dementia, which was most commonly defined according to the Diagnostic and Statistical Manual of Mental Disorders or National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria. Of the 24 studies that included a test of cognitive function, the most commonly used test was the Mini-Mental State Examination (MMSE).
    In most cases, the relationship between vitamin D and cognition was assessed by comparing mean vitamin D concentrations between patients diagnosed with dementia and controls or mean neuropsychological test scores between vitamin D groups.
    2 Meta-Analyses
    There were sufficient data to conduct 2 meta-analyses. The first compared the mean 25(OH)D concentration between AD and control groups. Six cross-sectional or case-control studies comparing data from 888 participants demonstrated a lower mean 25(OH)D concentration in patients with AD than in controls. The mean difference was −15.0 nmol/L (95% confidence interval [CI], −26.2 to −3.9 nmol/L).
    The researchers found that an important determinant of the statistically significant heterogeneity was the method of 25(OH)D measurement used. The competitive protein-binding assay (CPBA) explained the heterogeneity, but this method has been withdrawn from commercial use because of accuracy issues, said Dr. Balion.
    When the analysis was restricted to the 4 studies that used methods other than the CPBA, the overall difference between the AD and control groups was −6.2 nmol/L (95% CI, −10.6 to −1.8 nmol/L), with results consistent across studies. Similar results were found when studies comparing any dementia against a control group used methods other than the CPBA to measure vitamin D.
    Dr. Balion stressed the need for standardization of methods of measuring 25(OH)D and noted that relevant organizations are addressing this issue. In the meantime, it's important to consider the type of analytical method being used when comparing results from different studies, she said.
    Lack of true standardization is "a big problem in the field right now," commented Raj C. Shah, MD, a geriatrician and associate professor of family medicine, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois. "It's important to realize that all measurements of vitamin D are not equal."
    The second meta-analysis compared mean MMSE scores between participants with 25(OH)D concentrations less than 50 mmol/L and those with concentrations of 50 mmol/L or greater; 50 mmol/L is the most common cut-point reported in these studies and is often used to define vitamin D deficiency. Eight cross-sectional and case-control studies, which included data from 2749 participants, contributed to this analysis. Taken together, these studies showed a higher average MMSE score in participants with higher vitamin D concentrations.
    The average difference in MMSE score was 1.2 (95% CI, 0.5 to 1.9), although there was statistically significant heterogeneity. None of the subgroup analyses (for example, percentage of female participants, adjustment for at least age and sex) explained this heterogeneity.
    Dr. Balion noted that except for 2 studies, the average MMSE score of the groups was very similar. When 4 studies that used another type of cognitive screening tool were added, the results did not change substantially.
    Of the 2 cohort studies included in the analysis, the 1 that included only men reported no significant association between vitamin D and baseline cognitive impairment; in the other, however, participants with a deficiency in vitamin D had an increased risk for substantial cognitive decline over 6 years compared with those who had sufficient concentrations of the vitamin. As for the RCTs, the only study to use a supplement of vitamin D alone found no significant between-group differences for the single cognitive measure used.
    Comprehensive Analysis
    According to Dr. Balion, the results of this current review differ from those of 2 earlier ones because it was more comprehensive in its search strategy and in its inclusion criteria, which resulted in more articles screened (3229 vs 99 for a previous review). It also included more studies (37 vs 5 for the previous reviews). "We decided not to be limited in what we looked at," she said.
    Dr. Balion pointed out that some factors affecting vitamin D concentrations, including skin pigmentation, age, genetics, and time of sun exposure and testing, were not considered by some studies. As well, she said, reverse causation can't be ruled out because older people may have poor nutrition and spend less time exposed to sunlight, a major source of vitamin D. Despite these limitations, "I'm pretty happy saying that vitamin D plays a role in brain health," she said.
    How exactly vitamin D protects the brain is not clear, but research suggests that vitamin D acts as a neurosteroid, said Dr. Balion. At the molecular level, the brain can synthesize the active form of vitamin D [1,25(OH)D] within several cell types and regions, predominantly in the hypothalamus and large neurons in the substantia nigra. Many genes are regulated by vitamin D, which contributes to neuroprotection by modulating the production of such things as nerve growth factor, and regulating neurotransmitters.
    The ideal concentration of vitamin D is also not really known, said Dr. Balion. "We tried to assess that with the data that we had from all these papers, and some studies show there might be this magic cut point and other studies did not really find a cut point. Most studies aren't designed to look for that because they're not outcome studies."
    However, she noted that 2 cut points are recommended worldwide: 50 and 75 nmol/L. Canada, for example, recommends the upper level for bone health.
    Physicians should recommend supplements for patients not getting sufficient vitamin D, said Dr. Balion. Many jurisdictions, including Canada, recommend 600 IU of vitamin D daily for older children and adults; recommendations differ for younger children and pregnant women.
    Vitamin D Testing
    Ontario's universal healthcare system does not provide for vitamin D testing except for certain conditions (osteoporosis, osteopenia, rickets, malabsorption syndrome, renal disease, or taking medications that affect vitamin D metabolism) because the evidence is not yet established, said Dr. Balion.
    The United States has recommendations similar to Canada's, Dr. Shah notes. Americans are becoming more aware of vitamin D's health benefits and are taking more supplements; however, although the vitamin is fat soluble, and so may be safer than some other vitamins when taken at higher doses, Dr. Shah noted that it can still lead to muscle pains and gastrointestinal tract problems.
    When asked to comment on this review, Dr. Shah said, "it helps clinicians like me and researchers to understand where the state of science is in this field, and it tells us we have a lot more work to do." He noted that of the 37 papers included in the review, only a few were clinical trials.
    However, that may be changing. VITAL (VITamin D and OmegA-3 TriaL), a large 5-year clinical trial sponsored by the National Institutes of Health, is randomly assigning 20,000 people across the United States. The placebo-controlled trial will investigate whether vitamin D or omega fatty acid affects various aspects of health, including cognition.
    Dr. Shah raised several important issues pertaining to the analysis. For one thing, results of vitamin D studies may depend on where participants live and the time of the year that testing was done.
    He also noted that most studies were probably not done in diverse populations. "I suspect that subjects were mainly Caucasian," but because the United States has an increasingly diverse population, "we need to have measures of these effects in various older adults."
    Dr. Shah said that as with any meta-analysis, some publication bias probably exists, with negative studies not being published or available for review.
    He also questioned whether intervening through supplementation to arrive at a target vitamin D level would affect outcomes. He used the example of high-density lipoprotein, where experts believed that raising levels would reduce risks for heart disease. Preliminary research suggests that such efforts not only might not produce the expected result but also may cause some harm in terms of adverse effects.
    The study was funded by the Ontario Research Coalition of Research Institutes/Centers on Health & Aging, Ontario Ministry of Long-Term Care. Dr. Balion receives research support from the Canadian Institutes of Health Research, the Agency for Healthcare Research and Quality, the Canada Foundation for Innovation (CFI), and the Ontario Ministry of Health and Long-Term Care. For disclosures for other authors, see original paper. Dr. Shah has disclosed no relevant financial relationships.
    Neurology. 2012;79:1397-1405. Abstract

    Sunday, September 16, 2012

    Vitamin D research update

    Vitamin D and Parkinson'sA study from Finland suggested that higher vitamin D status provides protection against Parkinson's disease. People with the highest vitamin D levels (above 20 ng/mL) had a 65% lower risk of developing Parkinson disease than those with the lowest vitamin D levels (below 10 ng/mL).  

     Vitamin D and Alzheimer's
    A study in France among women 75 years of age and older found those with higher intakes of vitamin D from their diets least likely to develop Alzheimer’s disease over a seven-year study period.43 Women consuming more than 3,108 IU of vitamin per week (444 IU per day) were 77% less likely to develop Alzheimer’s disease than those with lower vitamin D intake. There was, however, no association between vitamin D intake and the risk of developing other types of dementia. The study excluded women who had taken vitamin D supplements.

    Vitamin D and Rheumatoid Arthritis
    Low levels of vitamin D are also associated with a higher risk in women of developing rheumatoid arthritis. There is conflicting evidence about whether vitamin D helps reduce the overall risk of dying from cancer, although studies have consistently shown that higher vitamin D serum levels were associated with decreased risk of death from gastrointestinal cancers.

    Vitamin D and Diabetes
    Vitamin D appears to reduce the risk of insulin resistance in obese individuals. Obesity itself is a major risk factor for insulin resistance, but too little vitamin D may increase the risk. A study found that obese individuals with vitamin D blood levels below 20 ng/mL were 12 times more likely to be insulin resistant than obese individuals with sufficient levels of vitamin D.41 The researchers suggest that insulin resistance in obese individuals may be reduced by making improvements in vitamin D levels.

    Having insulin resistance increases the risk of type 2 diabetes. So it is not surprising that a review of studies found that daily vitamin D intake over 500 IU decreased the risk of type 2 diabetes by 13% compared with intake of less than 200 IU. Similarly, individuals with vitamin D levels over 25 ng/mL had a 43% lower risk of developing type 2 diabetes compared to those with levels under 14 ng/mL. However, vitamin D supplementation has not been shown to affect glucose tolerance among people with established type 2 diabetes.23

    There is preliminary evidence that giving vitamin D supplements to infants might decrease the risk of type 1 diabetes later in life.

    23 Mitri, et al, Vitamin D and type 2 diabetes: a systematic review, Eur J Clin Nutr, 2011, 1-11

    41 Kabadi  Joint Effects of Obesity and Vitamin D Insufficiency on Insulin Resistance and Type 2 Diabetes: Results from the NHANES 2001-2006. ,  2012

    Friday, September 7, 2012

    It's Not the Red Wine, It's the Nitric Oxide!


    It's Not the Red Wine, It's the Nitric Oxide!

    This article inadvertently let the secret slip.  Blood pressure goes down as Nitric Oxide increases.  Take a look at the chart below.  But why does Nitric Oxide increase with red wine?  For one thing Resveratrol is made from red grape skin and is a major anti-oxidant.  Oxidation is a major scavenger of Nitric Oxide in the blood stream.  The more anti-oxidants you take the more Nitric Oxide you have available.  That's why there is Resveratrol and Pomegranate in ProArgi-9+.   

    Notice that alcoholic Red Wine reduces Nitric Oxide while nonalcoholic wine increases NO.  That's because of the alcohol.  Drinking red wine to lower your blood pressure is an advertising lie.   



    From Heartwire

    Nonalcoholic Red Wine Reduces Blood Pressure

    Sue Hughes
    September 7, 2012 (Barcelona, Spain) — Nonalcoholic red wine was associated with a greater reduction in blood pressure than regular red wine in a new study [1].
    The researchers, led by Dr Gemma Chiva-Blanch (University of Barcelona, Spain), conclude that the polyphenols found in red wine are the likely mediators of the blood-pressure reduction and that alcohol appears to weaken their antihypertensive effect.
    They suggest that daily consumption of nonalcoholic red wine may be useful for the prevention of mild to moderate hypertension.
    For the study, published online in Circulation Research on September 6, 2012, 67 men at high cardiovascular risk were randomized into three four-week treatment periods in a crossover clinical trial. Each participant followed a common background diet and also drank red wine (30 g alcohol/day), the equivalent amount of dealcoholized red wine, or gin (30 g alcohol/day). Blood pressure and plasma nitric-oxide (NO) concentration were measured at baseline and between each intervention. The men were moderate alcohol consumers before the study, but they abstained from drinking any alcohol for a two-week run-in period at the start of the study.
    Results showed that both systolic and diastolic blood pressure decreased significantly after the dealcoholized red wine intervention, and these changes correlated with increases in plasma NO. During the red-wine phase, the men had a small reduction in blood pressure and a small increase in NO, while there was no change in blood pressure and a small reduction in NO while drinking gin.
    Changes in blood pressure and nitric oxide with the different beverages
    Change in BP/NORed wineNonalcoholic red wineGin
    Systolic blood pressure (mm Hg)-2.3-5.8-0.8
    Diastolic blood pressure (mm Hg)-1.0-2.3-0.1
    Nitric oxide (┬Ámol/L)+0.6+4.1-1.4

    The researchers note that although the blood-pressure reduction associated with nonalcoholic red wine was modest, reductions of this magnitude have been associated with a 14% decrease in coronary heart disease and 20% reduction in stroke risk.

    Monday, June 25, 2012

    Does too much Vitamin D increase chances for Prostate Cancer?

     
    Question:

    I recently read about a study showing an INCREASE in prostate cancer in men supplementing with vitamin D. Is this true?

    Answer:
    It is true that a recently published study concluded "that men with higher vitamin D blood levels are at increased risk of developing prostate cancer." HOWEVER, a closer look at the data in this study showed that it only applied to men with very high calcium intake. Most other studies have not found this link and some lab studies have found vitamin D to inhibit prostate cancer cells.

    Thursday, March 15, 2012

    226% more oxidative stress with Statins.


    Thursday, March 15, 2012


    March 14, 2012, 12:01 AM

    Do Statins Make It Tough to Exercise?

    Can a statin ruin your workout?Epperson/Getty ImagesCan a statin ruin your workout?
    Phys Ed
    For years, physicians and scientists have been aware that statins, the most widely prescribed drugs in the world, can cause muscle aches and fatigue in some patients. What many people don’t know is that these side effects are especially pronounced in people who exercise.
    To learn more about the effect statins have on exercising muscles, scientists in Strasbourg, France, recently gave the cholesterol-lowering drug Lipitor to a group of rats for two weeks, while a separate control group was not medicated. Some of the rats from both groups ran on little treadmills until they were exhausted.
    It was immediately obvious that the medicated animals couldn’t run as far. They became exhausted much earlier than the rats that had not been given statins.
    Editor's note:
    Oxidative Stress is the single biggest scavenger of Nitric Oxide in the bloodstream. This is one of the reasons ProArgi-9+ has anti-oxidents, Resveratrol and pomegranate in the formula.  If statins increase oxidation by 226% imagine how much Nitric Oxide is being lost.  No wonder the test subjects were exhausted after exercise.

    The differences were even more striking at a cellular level. When the scientists studied muscle tissues, they found that oxidative stress, a measure of possible cell damage, was increased by 60 percent in sedentary animals receiving statins, compared with the unmedicated control group.
    The effect was magnified in the runners, whose cells showed 226 percent more oxidative stress than exercising animals that had not been given statins.

    Over all, the study data showed that working out while taking statins “exacerbated metabolic perturbations” in muscles, the study’s authors conclude. The drug made running harder and more damaging for the rats.
    The medicated running rats also had less glycogen or stored carbohydrates in their muscles than the unmedicated runners. And their mitochondria, tiny mechanisms within cells that generate power, showed signs of dysfunction; mitochondrial respiratory rates were about 25 percent lower than in the unmedicated runners.
    Statins’ safety has come under considerable scrutiny in recent weeks. Last month, the Food and Drug Administration added safety alerts to prescribing information for statins, warning of risks for memory loss and diabetes, as well as muscle pain. (Read more about those concerns here.)
    More than 20 million Americans are taking statins, and by most estimates, at least 10 percent of them will experience some degree of muscle achiness or fatigue. That proportion rises to at least 25 percent among people taking statins who regularly exercise, and may be 75 percent or higher among competitive athletes.
    Why and how exercise interacts with statins to cause muscle problems remains unknown, in part because it’s more difficult to study molecular responses in people than in animals. (People generally dislike muscle biopsies.) But an eye-opening 2005 study of healthy young people taking statins showed that the gene expression profiles in their leg muscles after exercising were very different from those of volunteers not using statins. In particular, genes associated with muscle building and repair were “down-regulated,” or expressed less robustly, in the group using statins.
    “It seems possible that statins increase muscle damage” during and after exercise “and also interfere somewhat with the body’s ability to repair that damage,” says Dr. Paul Thompson, the chief of cardiology at Hartford Hospital in Connecticut and senior author of the study.
    The finding creates a worrisome conundrum for patients and their doctors. Statin users typically are at high risk for cardiovascular problems, making them the very people who could most benefit from regular exercise. But it may be that as a result of muscle problems, some people taking statins exercise less or not at all. “Lower energy is linked to less interest in activity,” says Dr. Beatrice Golomb, an associate professor of medicine at the University of California, San Diego, who is studying exercise habits in statin users, “and fatigue with exertion is linked to less actual activity.”
    And less activity has its own consequences. Move less and you increase your risk of premature death and other undesirable outcomes, even if your cholesterol is under control.
    So what does the emerging science about statins and muscles mean for someone who is taking or considering the drugs? “Statins save lives,” Dr. Thompson says. “Most people cannot control their cholesterol with diet and exercise alone.” He advises athletes to stop taking the drugs several days before a competition or strenuous workout, to avoid exacerbating muscle damage. But if you have intractably high cholesterol or a history of heart disease or stroke, he says, “you should be on statins.”
    For people with lower heart disease risks, though, the benefits are equivocal. A 2010 study by Dr. Golomb and colleagues found that a majority of statin users reporting muscle problems “were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy.” The patients were not at high risk of dying from heart disease, but were suffering from sore muscles and potentially a more sedentary life.
    “Any indication of harm shifts the pendulum” toward risk, Dr. Golomb says, and should be considered before anyone decides whether to continue with statins.
    The good news is that “muscle aches almost always disappear as soon as someone stops using statins,” Dr. Thompson says, and your vascular system may have benefited in the meantime.
    “Statins are anti-aging for arteries,” he says. “If you take them, you’ll have younger arteries. Unfortunately,” he adds, “they are not anti-aging for muscles.”

    Tuesday, March 13, 2012

    Aspirin and Plavix treatment impair nitric oxide biosynthesis by platelets.

    Aspirin and clopidogrel (Plavix) treatment impair nitric oxide biosynthesis by platelets.
    O'Kane PD, Reebye V, Ji Y, Stratton P, Jackson G, Ferro A.
    Source


    Department of Clinical Pharmacology, Cardiovascular Division, 3.07 Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
    J Mol Cell Cardiol. 2008 Aug;45(2):223-9. Epub 2008 Jul 7.
    http://www.ncbi.nlm.nih.gov/pubmed/18606420 

    Abstract



    Aspirin and clopidogrel (Plavix) are used therapeutically for their anti-platelet effects. We examined the effects of aspirin and clopidogrel on basal and beta-adrenoceptor (beta-AR)-mediated platelet nitric oxide (NO) synthesis in healthy subjects and patients with coronary heart disease (CHD). Healthy subjects (n=19) were randomized in a double-blind cross-over manner to receive aspirin or clopidogrel, each at 75 mg daily, for 14 days. Patients (n=17) of similar age with CHD, taking aspirin, were randomized double-blind to either continue on aspirin 75 mg daily or to receive clopidogrel 75 mg daily for 14 days. NO synthase (NOS) activity was measured from l-[(3)H]arginine to l-[(3)H]citrulline conversion, and cGMP was determined by radioimmunoassay, in platelets basally and following incubation with isoproterenol or albuterol (each at 10(-5) mol/L).


    In healthy subjects, aspirin did not affect basal NOS activity or cGMP in platelets, but suppressed the normal increase in both by isoproterenol and albuterol. Clopidogrel suppressed platelet NOS activity and cGMP both basally and in response to beta-AR agonists. In platelets from CHD patients, clopidogrel suppressed basal and beta-AR-stimulated NOS activity and cGMP as compared with aspirin. Platelet NOS activity and cGMP were lower in CHD subjects pre-randomization compared with healthy subjects both pre-randomization and post-aspirin. 


    We conclude that chronic aspirin treatment suppresses beta-AR-stimulated but not basal platelet NO synthesis, as previously described, whereas chronic clopidogrel (Plavix) treatment suppresses both, with resultant functional consequences. Moreover, CHD may itself be associated with decreased platelet NO biosynthesis.




    PMID:
    18606420
    [PubMed - indexed for MEDLINE]

    Men who love soda at higher risk for heart attack, say Harvard scientists; Sugary drink habit could kill

    Drinking two sugary beverages a day increases cardiac risk by 42%

    Experts have some not-so-sweet news for men who drink sodas and sugary drinks.
    Downing just one sugary beverage a day can up your heart attack risk by 20%, according to research published by Harvard scientists in the journal Circulation.
    The more soda or noncarbonated fruity drinks, the higher your risk.
    Two servings ups your heart risk by 42%. Drink a soda with all three meals? Your risk increases by 69%.
    The team of Harvard researchers found a strong correlation between sugary drinks and heart attack risk that held up even after factoring in smoking, physical activity, alcohol, family history and BMI, reports MSNBC.com.
    Volunteers who kicked their soda and sweet-drink habits experienced lower blood pressure.
    While this study didn’t take diet soda into account, recent studies have linked artificially sweetened drinks to increased stroke and heart attack risk.
    While this research focused on men, researchers say, sweet drinks aren’t good for women either.
    It’s a problem that can easily be solved if people just stopped sipping the high calorie beverages and paid more attention to what they’re imbibing, according to lead study author, Lawrence de Koning, a research fellow in the department of nutrition at the Harvard School of Public Health.
    “The first thing to do is to reduce the intake of sodas and then eventually eliminate them,” he said.






    • Original Research Article

    Sweetened Beverage Consumption, Incident Coronary Heart Disease and Biomarkers of Risk in Men

    1. Lawrence de Koning1
    2. Vasanti S. Malik2
    3. Mark D. Kellogg3;
    4. Eric B. Rimm4
    5. Walter C. Willett4
    6. Frank B. Hu4*
    +Author Affiliations
    1. 1 Harvard School of Public Health & Children's Hospital Boston, Boston MA;
    2. 2 Harvard School of Public Health, Boston, MA;
    3. 3 Children's Hospital Boston, Boston MA;
    4. 4 Harvard School of Public Health & Medical School & Brigham and Women's Hospital, Boston, MA
    1. * Corresponding author; email: fhu@hsph.harvard.edu

    Abstract

    Background—Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes. Few studies have tested for a relationship with coronary heart disease (CHD), or intermediate biomarkers. The role of artificially sweetened beverages is also unclear.
    Methods and Results—We performed an analysis of the Health Professionals Follow-up study, a prospective cohort study including 42 883 men. Associations of cumulatively averaged sugar-sweetened (e.g. sodas) and artificially sweetened (e.g. diet sodas) beverage intake with incident fatal and non-fatal CHD (myocardial infarction) were examined using proportional hazard models. There were 3683 CHD cases over 22 years of follow-up. Participants in the top quartile of sugar-sweetened beverage intake had a 20% higher relative risk of CHD than those in the bottom quartile (RR=1.20, 95% CI: 1.09, 1.33, p for trend < 0.01) after adjusting for age, smoking, physical activity, alcohol, multivitamins, family history, diet quality, energy intake, BMI, pre-enrollment weight change and dieting. Artificially sweetened beverage consumption was not significantly associated with CHD (multivariate RR=1.02, 95% CI: 0.93, 1.12, p for trend = 0.28). Adjustment for self-reported high cholesterol, high triglycerides, high blood pressure and diagnosed type 2 diabetes slightly attenuated these associations. Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased triglycerides, CRP, IL6, TNFr1, TNFr2, decreased HDL, Lp(a), and leptin (p values < 0.02).
    Conclusions—Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids, inflammatory factors, and leptin. Artificially sweetened beverage intake was not associated with CHD risk or biomarkers.