December 8, 2010 (Dallas, Texas)— The second study in a month to find that detection of cardiac troponin T--as measured by high-sensitivity assays--is associated with all-cause mortality raises the possibility that testing troponin as a chronic marker of cardiovascular disease might one day become routine in the doctor's office, say the researchers, who publish their findings in the December 8, 2010 issue of the Journal of the American Medical Association [1].
Dr James A de Lemos (University of Texas Southwestern Medical Center, Dallas) and colleagues followed a relatively young population of 30- to 65-year-olds and found that troponin was detectable in approximately 25% of people and was associated with structural heart disease and risk of subsequent all-cause mortality. The findings complement those of a second study, by Dr Christopher R deFilippi (University of Maryland School of Medicine, Baltimore) et al, appearing in the same issue of the journal but published online last month to coincide with a presentation at the American Heart Association meeting. It showed cardiac troponin T detected by high-sensitivity assay was associated with new-onset heart failure and cardiovascular death in adults aged 65 and over.
"The message is that we might have to rethink the way we have considered troponin and perhaps use it more as a chronic marker for disease than as an acute marker of someone having a heart attack. There is a possibility troponin could be used as a screening test," de Lemos told heartwire.
Two Studies Are Better Than One
We might have to rethink the way we have considered troponin and use it more as a chronic marker for disease than as an acute marker of heart attack.
Although raised troponin levels as detected by traditional assays have long been used to indicate myocardial infarction (MI), a new analysis from the PEACE trial published last year showed that almost any troponin detected by high-sensitivity tests was associated with heart failure and death in a stable coronary heart disease population. The new papers are the first to show the same outcome in two general populations without underlying cardiovascular disease, across a wide age spectrum.
"These are highly complementary studies published side-by-side for that reason," de Lemos explained. "Validation is the key to knowing whether results are real or spurious. The mortality findings across the studies are similar." He points out also that the two papers cover different age groups, further strengthening the findings, and that each has its own unique feature: in his own, the detailed assessments done by cardiac magnetic resonance imaging (MRI), and in the other study, the availability of serial measurements of troponin.
Taken together, these new studies and the PEACE analysis from last year "suggest important differences in the pathophysiology of troponin release in the chronic compared with the acute setting," say he and his colleagues.
Adding Troponin Modestly Improved Mortality Models
In their study, de Lemos et al measured troponin levels using both the traditional and new highly sensitive assays (which detect around 10-fold lower levels than standard assays) in 3546 individuals enrolled between 2000 and 2002 in the Dallas Heart Study, a multiethnic population-based cohort with a large proportion of women. The main outcome measures were MRI of cardiac structure and function and mortality through a median of 6.4 years of follow-up.
The prevalence of detectable cardiac troponin T (>0.003 ng/mL) was 25% with the highly sensitive assay vs 0.7% with the standard assay. Prevalence was 37.1% in men vs 12.9% in women and 14% in those younger than 40 vs 57.6% in those 60 and over.
Participants were placed into five categories based on troponin levels. Prevalence of LV hypertrophy increased from 7.5% in the lowest troponin category (<0.003 ng/mL) to 48.1% in the highest (>0.014 ng/mL; p<0.001); prevalence of LV systolic dysfunction and chronic kidney disease also increased across categories (p<0.001 for each).
There were 151 total deaths, including 62 CVD deaths. All-cause mortality increased from 1.9% to 28.4% across higher troponin categories. After adjustment for traditional risk factors, C-reactive protein (CRP), chronic kidney disease, and N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin remained independently associated with all-cause mortality (adjusted HR 2.8). Adding troponin categories to the fully adjusted mortality model modestly improved model fit (p=0.02) and the integrated discrimination index (p=0.01).
"Our study gives us a mechanism by which the elevation of troponin might be working; it helps explain the 'why' for the heart-failure mortality, which, in many ways, makes perfect sense, because troponin is a structural cardiac protein," says de Lemos.
Education to Aid Doctors in Use of Highly Sensitive Troponin Assays
The results suggest that future studies should be performed to assess whether measurement of troponin with a highly sensitive assay adds value to traditional cardiovascular risk factors as well as measures of renal function and NT-proBNP for risk assessment in the general population, say de Lemos and colleagues.
And the independent and additive associations of troponin and NT-proBNP observed "suggest that combinations of these two markers may perform better than either marker alone," they add.
They note also that this new research has important implications for the use of highly sensitive assays in the hospital, with work needed to educate doctors to avoid false-positive diagnoses of acute MI.
These new highly sensitive assays may add trouble and confusion in the ER but open a whole new world in the doctor's office.
Although de Lemos says there are some obvious indicators that troponin detection is due to MI rather than a chronic, underlying condition--for example, the magnitude of elevation, where "very, very high levels of troponin will still indicate MI," and use of serial measurements to look for acute rises in troponin--this will be "an imperfect science," and not nearly as simple as people might think.
"In Europe, where they are using these new assays, they are setting a higher threshold to diagnose MI that is similar to the old threshold. But then, how do you interpret a value between the old level and new level? We need algorithms. Troponin has always been a yes/no test for a heart attack. These new highly sensitive assays may add trouble and confusion in the ER but open a whole new world in the doctor's office," he concludes.
de Lemos has received research grants from Roche Diagnostics and Biosite/Inverness and consulting fees and/or lecture honoraria from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Inverness, Siemens, AstraZeneca, Pfizer, Bristol-Myers Squibb/Sanofi-Aventis, and Merck/Schering. Disclosures for the coauthors are listed in the paper.
References
1.de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 2010; 304:2503-2512.
Saturday, December 11, 2010
Friday, December 10, 2010
how people die
Stroke has dropped from third to fourth place in the leading causes of U.S. deaths, according to a preliminary CDC report on mortality data from 2008. Rounding out the top five are heart disease (1), cancer (2), chronic lower respiratory diseases (3), and accidents (5).
The number of stroke deaths fell by roughly 20% from 2000 to 2008. American Heart Association president Dr. Ralph L. Sacco says that the reduction can be attributed to a combination of improved prevention, greater use of thrombolytics, and use of drugs that prevent recurrent stroke.
Meanwhile, deaths from chronic lower respiratory diseases increased, partly due to a change in the WHO's classification system.
In addition, American life expectancy decreased slightly, from 77.9 years in 2007 to 77.8 years in 2008.
The number of stroke deaths fell by roughly 20% from 2000 to 2008. American Heart Association president Dr. Ralph L. Sacco says that the reduction can be attributed to a combination of improved prevention, greater use of thrombolytics, and use of drugs that prevent recurrent stroke.
Meanwhile, deaths from chronic lower respiratory diseases increased, partly due to a change in the WHO's classification system.
In addition, American life expectancy decreased slightly, from 77.9 years in 2007 to 77.8 years in 2008.
Tuesday, December 7, 2010
Longer Sleep Duration Linked to Lower Risk for Coronary Artery Calcification
MAYBE DUE TO LOWER CORTICOSTEROIDS IE INCREASED CORTISOL RELEASE IN SLEEP DEPRIVED PEOPLE
Middle-aged adults who get more sleep each night may face lower risk for coronary artery calcification, according to an observational study in JAMA.
Some 500 adults aged 35 to 47 without calcification were followed for 5 years. During that time, sleep data were collected in two separate years, for six nights total, with use of wrist-activity monitors.
Calcification developed in 12% of the participants during follow-up. After adjustment for confounders such as age, smoking, and other cardiovascular risk factors, the odds of calcification were 34% lower with each additional hour of sleep per night — an effect equivalent to that of a 16.5-mm Hg drop in systolic blood pressure, the authors note.
They conclude that whether the association between sleep duration and coronary artery calcification translates into a reduction in coronary disease events remains to be determined.
Middle-aged adults who get more sleep each night may face lower risk for coronary artery calcification, according to an observational study in JAMA.
Some 500 adults aged 35 to 47 without calcification were followed for 5 years. During that time, sleep data were collected in two separate years, for six nights total, with use of wrist-activity monitors.
Calcification developed in 12% of the participants during follow-up. After adjustment for confounders such as age, smoking, and other cardiovascular risk factors, the odds of calcification were 34% lower with each additional hour of sleep per night — an effect equivalent to that of a 16.5-mm Hg drop in systolic blood pressure, the authors note.
They conclude that whether the association between sleep duration and coronary artery calcification translates into a reduction in coronary disease events remains to be determined.
Monday, November 8, 2010
Invasive Dental Treatment Linked to Vascular Events?
Invasive dental treatment might be associated with a short-term increase in vascular risk, according to a self-controlled study in the Annals of Internal Medicine.
Using Medicaid databases, researchers identified some 1200 adults who both underwent invasive dental procedures (e.g., periodontal therapy, extractions) and also experienced a myocardial infarction or stroke from 2002 to 2006. They found that vascular events were more common in the month after dental treatment than at other times during the observation period (incidence ratio, 1.5). Risk gradually returned to baseline by 6 months after dental treatment.
The authors point to acute inflammation as a potential underlying mechanism. They add that "the absolute risks are minimal, and the long-term benefits on vascular health will probably outweigh the short-lived adverse effects." Meanwhile, editorialists say the study is "an important reminder to continue cardioprotective antiplatelet agents if at all possible before and after dental procedures in patients who are receiving these agents."
Using Medicaid databases, researchers identified some 1200 adults who both underwent invasive dental procedures (e.g., periodontal therapy, extractions) and also experienced a myocardial infarction or stroke from 2002 to 2006. They found that vascular events were more common in the month after dental treatment than at other times during the observation period (incidence ratio, 1.5). Risk gradually returned to baseline by 6 months after dental treatment.
The authors point to acute inflammation as a potential underlying mechanism. They add that "the absolute risks are minimal, and the long-term benefits on vascular health will probably outweigh the short-lived adverse effects." Meanwhile, editorialists say the study is "an important reminder to continue cardioprotective antiplatelet agents if at all possible before and after dental procedures in patients who are receiving these agents."
Thursday, September 23, 2010
Avoid Stenting for Carotid Stenosis in Those 70 and Older, Meta-Analysis Suggests
Stenting in patients with symptomatic carotid stenosis should be avoided in those aged 70 and older, according to a Lancet meta-analysis.
Investigators from three randomized trials, seeking to reconcile disparate findings on the risks of treatment with endarterectomy versus stenting, undertook a preplanned meta-analysis of their data. Their trials comprised some 3400 patients with symptomatic stenosis who were judged to be at standard surgical risk.
In both the intention-to-treat group (analyzed at 120 days) and per-protocol group (analyzed at 30 days), patients under age 70 showed no difference in risk for the primary outcome (the combination of any stroke or death), regardless of the therapy. In those 70 and older, however, stenting was associated with a doubling of risk.
The authors conclude their findings provide "strong evidence that, in the short term, the harm of stenting compared with endarterectomy decreases with younger age."
Investigators from three randomized trials, seeking to reconcile disparate findings on the risks of treatment with endarterectomy versus stenting, undertook a preplanned meta-analysis of their data. Their trials comprised some 3400 patients with symptomatic stenosis who were judged to be at standard surgical risk.
In both the intention-to-treat group (analyzed at 120 days) and per-protocol group (analyzed at 30 days), patients under age 70 showed no difference in risk for the primary outcome (the combination of any stroke or death), regardless of the therapy. In those 70 and older, however, stenting was associated with a doubling of risk.
The authors conclude their findings provide "strong evidence that, in the short term, the harm of stenting compared with endarterectomy decreases with younger age."
Friday, August 20, 2010
Green Leafy Vegetables Seem to Lower Diabetes Risk
Increased consumption of leafy green vegetables is associated with lower risk for developing type 2 diabetes, a BMJ meta-analysis finds.
Researchers examined data from six prospective cohort studies that measured individual consumption of fruits and vegetables. The studies also assessed the development of diabetes over a median of 13 years. Intake of fruit or vegetables, either alone or combined, was not associated with lower risk. In the four studies that specifically measured the intake of leafy green vegetables, a 14% reduction in diabetes risk was apparent between the highest and lowest levels of consumption.
The authors cite the antioxidant effects of beta-carotene, polyphenols, and vitamin C as possible mechanisms for this effect. Editorialists comment that dietary advice "may be just as beneficial, if not more so, than prescribing drugs" to patients at risk.
Researchers examined data from six prospective cohort studies that measured individual consumption of fruits and vegetables. The studies also assessed the development of diabetes over a median of 13 years. Intake of fruit or vegetables, either alone or combined, was not associated with lower risk. In the four studies that specifically measured the intake of leafy green vegetables, a 14% reduction in diabetes risk was apparent between the highest and lowest levels of consumption.
The authors cite the antioxidant effects of beta-carotene, polyphenols, and vitamin C as possible mechanisms for this effect. Editorialists comment that dietary advice "may be just as beneficial, if not more so, than prescribing drugs" to patients at risk.
Wednesday, July 14, 2010
alzheimers, no prevention absolutely known
"There is currently no evidence of even moderate scientific quality supporting the association of any modifiable factor ... with reduced risk of Alzheimer's disease," a panel convened by the National Institutes of Health concluded on Wednesday. Evidence for measures to prevent cognitive decline is "similarly limited," the panel said.
The factors in question include intake of dietary supplements, use of prescription and nonprescription drugs, diet, physical activity, and social engagement.
The panel added that despite the limited evidence regarding cognitive decline, some of the measures "are not necessarily harmful and may confer other benefits."
The factors in question include intake of dietary supplements, use of prescription and nonprescription drugs, diet, physical activity, and social engagement.
The panel added that despite the limited evidence regarding cognitive decline, some of the measures "are not necessarily harmful and may confer other benefits."
Wednesday, June 2, 2010
The problem with medical studies
Aspirin Recommended as Preventive for Cardiovascular Events in Diabetics
Low-dose aspirin (75 to 162 mg/day) is a "reasonable" choice for adults with diabetes who have a 10-year risk for cardiovascular disease above 10% and are not at increased risk for bleeding, according to a statement from the American Diabetes Association, the American Heart Association, and the American College of Cardiology.
The statement, published in Circulation, is based on meta-analysis of nine trials examining the effects of aspirin to prevent cardiovascular disease events in patients with diabetes. It also recommends the following:
Adults with diabetes who are at increased risk for cardiovascular disease (e.g., men over 50 or women over 60 with an additional CVD risk factor) should receive aspirin for primary prevention.
Patients at intermediate risk for cardiovascular disease (e.g., younger patients with at least one risk factor, older patients with no risk factors, or patients with a 10-year risk of 5% to 10%) may consider taking daily aspirin.
Low-dose aspirin (75 to 162 mg/day) is a "reasonable" choice for adults with diabetes who have a 10-year risk for cardiovascular disease above 10% and are not at increased risk for bleeding, according to a statement from the American Diabetes Association, the American Heart Association, and the American College of Cardiology.
The statement, published in Circulation, is based on meta-analysis of nine trials examining the effects of aspirin to prevent cardiovascular disease events in patients with diabetes. It also recommends the following:
Adults with diabetes who are at increased risk for cardiovascular disease (e.g., men over 50 or women over 60 with an additional CVD risk factor) should receive aspirin for primary prevention.
Patients at intermediate risk for cardiovascular disease (e.g., younger patients with at least one risk factor, older patients with no risk factors, or patients with a 10-year risk of 5% to 10%) may consider taking daily aspirin.
CREST Trial Points to Endarterectomy as Preferred Stroke Preventive Strategy
A comparison of endarterectomy versus stenting in treating carotid artery stenosis shows that stent recipients are at higher risk for stroke within 30 days of the procedure, according to a New England Journal of Medicine study released online.
Investigators in the CREST trial randomized some 2500 patients with carotid artery stenosis to either stenting or endarterectomy. After a median follow-up of 2.5 years, the groups showed no significant difference in the primary endpoint — a composite of stroke, myocardial infarction, or death from any cause during the periprocedural period, or ipsilateral stroke within 4 years.
However, the 4-year rate of stroke or death significantly favored endarterectomy. When the individual outcomes were examined, there were significantly more periprocedural strokes after stenting, and more MIs after endarterectomy.
Editorialists conclude that "endarterectomy remains the preferred treatment for most patients."
Investigators in the CREST trial randomized some 2500 patients with carotid artery stenosis to either stenting or endarterectomy. After a median follow-up of 2.5 years, the groups showed no significant difference in the primary endpoint — a composite of stroke, myocardial infarction, or death from any cause during the periprocedural period, or ipsilateral stroke within 4 years.
However, the 4-year rate of stroke or death significantly favored endarterectomy. When the individual outcomes were examined, there were significantly more periprocedural strokes after stenting, and more MIs after endarterectomy.
Editorialists conclude that "endarterectomy remains the preferred treatment for most patients."
Sunday, April 11, 2010
NACL PROTECTS AGAINST PREMATURE DEATH NHANES 2
Another what bites the dust? Another one of the shibboleths of “healthy living” that the nutritional establishment has been pounding us over our heads with for decades: the idea that salt is bad for us.
Now, in the wake of the three Woman’s Health Initiative studies showing that fat doesn’t seem to cause heart disease nor cancers or the breast or colon, comes a study from the venerable NHANES II data showing that not only does salt intake (or to be more precise, sodium intake) not cause premature death from heart disease it actually seems to protect against it. And consuming more sodium appears to protect against premature deaths from not just heart disease but from all other causes as well. It’s been a bad couple of weeks for the holier-than-thou crowd.
In the current issue of The American Journal of Medicine is a study filled with much interesting information that gives a peephole into the way the pinheads in the government issue edicts that affect the health of all those ignorant enough to abide by them. This study shows that the subjects who consumed the least sodium in the late 1970s had greater rates of death from cardiovascular disease and from all other causes than those who consumed more sodium. Before we delve into all that, however, let’s look at what the paper shows about how government works.
The US Department of Health and Human Services and the US Department of Agriculture 2005 nutritional guidelines (click here to read in full in a large pdf download) recommend that Americans consume less than 2300 mg of sodium per day (which is less than the 2400 mg recommended in the 2000 guidelines) in order to “prevent or delay the onset of high blood pressure..” and “to lower elevated blood pressure” Seems rationale enough until one considers that there is really no good evidence that sodium intake causes blood pressure to increase other than that shown in short-term clinical trials, a number of which are inconclusive or contradictory. It’s just like with the idea of low-fat: somewhere, sometime, someone got it into his or her head that dietary sodium is bad, the word spread, and researchers start doing studies to prove it. As long as a study here or there confirms this bias, then the idea is held in the minds of many people not simply as an hypothesis, but as a truth. In the case of the nutritional guidelines, the scientific committee making recommendations did so
largely based on the blood pressure reduction associated with lower sodium in short-term clinical trials. However, these trials could not assess the long-term cardiovascular morbidity and mortality consequences of lower sodium. Of concern is that lower sodium intake can generate increased activity of the renin-angiotensin and sympathetic nervous systems, and possibly increased insulin resistance, and each of these could have adverse cardiovascular effects. Morbidity and mortality outcomes will be influenced by unfavorable and favorable effects, as well as the unknown consequences of a diet altered to achieve lower sodium intake. In the absence of clinical trial data, several observational studies, with contradictory results, are available.
So, it’s not even really a case of unintended consequences. The scientific committee chose to overlook evidence clearly showing that there could easily be a downside to sodium restriction in favor of their built-in bias against salt. In fact, based on no good evidence they lowered the recommendation from that of the time before. Gives one a lot of faith in the nutritional guidelines, doesn’t it?
Basically here is how the study was done. Researchers used the data from NHANES II study (a large pdf of the NHANES II study can be downloaded by clicking here) to determine if sodium intake correlated with premature death. The NHANES II researchers interviewed and examined participants and collected data in 1976-1980. The nutrient intake data came from one 24 hour recall done by trained interviewers, which isn’t as good as a 3 or 4 day food diary, but is better that a food frequency questionnaire. The study was followed up by evaluating the mortality statistics as of December 31, 1992 to determine the numbers of deaths in the study subjects and their causes. As the researchers put it in reference to these study subjects without a hint of tongue in cheek:
Those not found to be deceased were assumed alive at that date.
Indeed. I wonder if there were another choice.
The researchers set the breakpoint of their data analysis at the 2300 mg of sodium recommended in the nutritional guidelines. After analyzing the nutritional and mortality data on this basis it turned out that those subjects who consumed less than 2300 mg of sodium per day had a 1.37 times increased risk (95% CI 1.03-1.81, P=.033) of dying from heart disease and a 1.28 times increased risk (95% CI 1.1-1.5, P=.003) of dying from all causes as compared to those who consumed more than 2300 mg of sodium per day.
As the authors of the study put it:
The principal finding in this representative sample of US adults is that sodium intake, measured as a continuous variable and adjusted for calories by each of three distinct methods, had a statistically significant and inverse association with CVD mortality, independent of known cardiovascular risk factors. Results were consistent for all-cause, CHD, and cerebrovascular-specific mortality, although these latter associations were not statistically significant. In addition, individuals reporting consumption of sodium consistent with the most recent US dietary guidelines of
Makes you glad you spent all that time watching your salt doesn’t it?
I have a little different take on the results of this study from a statistical standpoint. Harkening back to the long and complex post about confidence intervals a while back you might remember that the parenthetical expression after the risk ratio shows what the range is statistically with 95% confidence that it will actually fall in that range. In the case above for the cardiovascular mortality risk of 1.37 what those figures actually mean is that there is a 95% probability (not 100%) that the actual risk will fall into the range of 1.03 to 1.81. In other words we can say that with 95% confidence if you consume less than 2300 mg of sodium per day you have somewhere in the range of 1.03 to 1.81 times greater risk of dying prematurely from heart disease than if you consume more than 2300 mg of sodium per day.
Because of the 5% uncertainty (100% minus 95%) and the fact that it could just as easily be the 1.03 figure as the 1.81 figure for risk I don’t like to take these things as gospel unless the risk ratio is at least 2.0. But that’s just me. Others who are less statistically nit picky are more than happy to go with the lower risk ratios.
Based on my more statistically rigid interpretation of the data, I can conclude that at the very least it doesn’t make any difference how much sodium you consume. To me, that’s the take home message.
Oh, one other take home message: don’t believe scientific committees. In the discussion part of this paper the authors laid out a sampling of studies looking at sodium intake verses disease:
Eight previous observational studies examined clinical outcomes associated with sodium levels. Sodium intake was inversely and significantly associated with higher CVD mortality for the entire sample of NHANES I, with myocardial infarction among male participants in a prospective cohort study of treated hypertensives and with all-cause mortality in men in the Scottish Heart Study. By contrast, a statistically significant direct association of sodium with CVD and all-cause mortality was observed in a Finnish community sample, among the overweight subset of NHANES I, with CHD incidence among women in the Scottish study, and with stroke in a community sample in Japan. No statistically significant associations were reported either among Japanese-American men of the Honolulu Heart Study or in the MRFIT cohort.
All these studies were done and published long before the scientific committee made their recommendations for the nutritional guidelines and were inconsistent and inconclusive at best, so how could the recommendation to lower sodium even further be even contemplated much less done? Bias. Or its synonym prejudice.
Ambrose Bierce (one of my favorite writers) defined prejudice as:
A vagrant opinion without visible means of support.
Please pass the salt.
Now, in the wake of the three Woman’s Health Initiative studies showing that fat doesn’t seem to cause heart disease nor cancers or the breast or colon, comes a study from the venerable NHANES II data showing that not only does salt intake (or to be more precise, sodium intake) not cause premature death from heart disease it actually seems to protect against it. And consuming more sodium appears to protect against premature deaths from not just heart disease but from all other causes as well. It’s been a bad couple of weeks for the holier-than-thou crowd.
In the current issue of The American Journal of Medicine is a study filled with much interesting information that gives a peephole into the way the pinheads in the government issue edicts that affect the health of all those ignorant enough to abide by them. This study shows that the subjects who consumed the least sodium in the late 1970s had greater rates of death from cardiovascular disease and from all other causes than those who consumed more sodium. Before we delve into all that, however, let’s look at what the paper shows about how government works.
The US Department of Health and Human Services and the US Department of Agriculture 2005 nutritional guidelines (click here to read in full in a large pdf download) recommend that Americans consume less than 2300 mg of sodium per day (which is less than the 2400 mg recommended in the 2000 guidelines) in order to “prevent or delay the onset of high blood pressure..” and “to lower elevated blood pressure” Seems rationale enough until one considers that there is really no good evidence that sodium intake causes blood pressure to increase other than that shown in short-term clinical trials, a number of which are inconclusive or contradictory. It’s just like with the idea of low-fat: somewhere, sometime, someone got it into his or her head that dietary sodium is bad, the word spread, and researchers start doing studies to prove it. As long as a study here or there confirms this bias, then the idea is held in the minds of many people not simply as an hypothesis, but as a truth. In the case of the nutritional guidelines, the scientific committee making recommendations did so
largely based on the blood pressure reduction associated with lower sodium in short-term clinical trials. However, these trials could not assess the long-term cardiovascular morbidity and mortality consequences of lower sodium. Of concern is that lower sodium intake can generate increased activity of the renin-angiotensin and sympathetic nervous systems, and possibly increased insulin resistance, and each of these could have adverse cardiovascular effects. Morbidity and mortality outcomes will be influenced by unfavorable and favorable effects, as well as the unknown consequences of a diet altered to achieve lower sodium intake. In the absence of clinical trial data, several observational studies, with contradictory results, are available.
So, it’s not even really a case of unintended consequences. The scientific committee chose to overlook evidence clearly showing that there could easily be a downside to sodium restriction in favor of their built-in bias against salt. In fact, based on no good evidence they lowered the recommendation from that of the time before. Gives one a lot of faith in the nutritional guidelines, doesn’t it?
Basically here is how the study was done. Researchers used the data from NHANES II study (a large pdf of the NHANES II study can be downloaded by clicking here) to determine if sodium intake correlated with premature death. The NHANES II researchers interviewed and examined participants and collected data in 1976-1980. The nutrient intake data came from one 24 hour recall done by trained interviewers, which isn’t as good as a 3 or 4 day food diary, but is better that a food frequency questionnaire. The study was followed up by evaluating the mortality statistics as of December 31, 1992 to determine the numbers of deaths in the study subjects and their causes. As the researchers put it in reference to these study subjects without a hint of tongue in cheek:
Those not found to be deceased were assumed alive at that date.
Indeed. I wonder if there were another choice.
The researchers set the breakpoint of their data analysis at the 2300 mg of sodium recommended in the nutritional guidelines. After analyzing the nutritional and mortality data on this basis it turned out that those subjects who consumed less than 2300 mg of sodium per day had a 1.37 times increased risk (95% CI 1.03-1.81, P=.033) of dying from heart disease and a 1.28 times increased risk (95% CI 1.1-1.5, P=.003) of dying from all causes as compared to those who consumed more than 2300 mg of sodium per day.
As the authors of the study put it:
The principal finding in this representative sample of US adults is that sodium intake, measured as a continuous variable and adjusted for calories by each of three distinct methods, had a statistically significant and inverse association with CVD mortality, independent of known cardiovascular risk factors. Results were consistent for all-cause, CHD, and cerebrovascular-specific mortality, although these latter associations were not statistically significant. In addition, individuals reporting consumption of sodium consistent with the most recent US dietary guidelines of
Makes you glad you spent all that time watching your salt doesn’t it?
I have a little different take on the results of this study from a statistical standpoint. Harkening back to the long and complex post about confidence intervals a while back you might remember that the parenthetical expression after the risk ratio shows what the range is statistically with 95% confidence that it will actually fall in that range. In the case above for the cardiovascular mortality risk of 1.37 what those figures actually mean is that there is a 95% probability (not 100%) that the actual risk will fall into the range of 1.03 to 1.81. In other words we can say that with 95% confidence if you consume less than 2300 mg of sodium per day you have somewhere in the range of 1.03 to 1.81 times greater risk of dying prematurely from heart disease than if you consume more than 2300 mg of sodium per day.
Because of the 5% uncertainty (100% minus 95%) and the fact that it could just as easily be the 1.03 figure as the 1.81 figure for risk I don’t like to take these things as gospel unless the risk ratio is at least 2.0. But that’s just me. Others who are less statistically nit picky are more than happy to go with the lower risk ratios.
Based on my more statistically rigid interpretation of the data, I can conclude that at the very least it doesn’t make any difference how much sodium you consume. To me, that’s the take home message.
Oh, one other take home message: don’t believe scientific committees. In the discussion part of this paper the authors laid out a sampling of studies looking at sodium intake verses disease:
Eight previous observational studies examined clinical outcomes associated with sodium levels. Sodium intake was inversely and significantly associated with higher CVD mortality for the entire sample of NHANES I, with myocardial infarction among male participants in a prospective cohort study of treated hypertensives and with all-cause mortality in men in the Scottish Heart Study. By contrast, a statistically significant direct association of sodium with CVD and all-cause mortality was observed in a Finnish community sample, among the overweight subset of NHANES I, with CHD incidence among women in the Scottish study, and with stroke in a community sample in Japan. No statistically significant associations were reported either among Japanese-American men of the Honolulu Heart Study or in the MRFIT cohort.
All these studies were done and published long before the scientific committee made their recommendations for the nutritional guidelines and were inconsistent and inconclusive at best, so how could the recommendation to lower sodium even further be even contemplated much less done? Bias. Or its synonym prejudice.
Ambrose Bierce (one of my favorite writers) defined prejudice as:
A vagrant opinion without visible means of support.
Please pass the salt.
mammograms before 50 in healthy women=useless?
50 000 plus healthy woman were split into 2 groups. One group had yearly mammograms and breast exams for 5 years while the other group had breast exams/mammograms if the doctor thought it prudent. The numbers of invasive (cancer that had spread into surrounding areas) and in situ (cancer that had not spread) cancers were similar in both groups. These results suggest that mammograms and regular breast examinations do not reduce breast cancer deaths. The power of the study could not detect if ther differences were less than 20%. Annals 2002 137: 305-312-http://www.annals.org/cgi/content/full/137/5_Part_1/I-28?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=mammograms&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
Understanding significance in science
Consider a fixed die such that on average after 61 rolls the outcomes are 11 sixes and 10 of the remaining integers one through five. How many rolls would it take to determine with 95 % certainty that the die was biased? Meta-analysis studies (who get a final p value less than 0.05 ie significant)often take smaller studies with a p value greater than 0.05 (ie insignificant) and combine them to get a to big enough sample to determine significance. Due to picking one study and excluding another, one could get different answers to the same question. The cochrane collaboration tries to set criteria for w/c studies are to be included before performing the meta-analysis thereby avoiding some bias.
Fat/smokers excellent citizens
Fat People Cheaper to Treat, Study Says
By MARIA CHENG – 1 day ago
LONDON (AP) — Preventing obesity and smoking can save lives, but it doesn't save money, researchers reported Monday. It costs more to care for healthy people who live years longer, according to a Dutch study that counters the common perception that preventing obesity would save governments millions of dollars.
"It was a small surprise," said Pieter van Baal, an economist at the Netherlands' National Institute for Public Health and the Environment, who led the study. "But it also makes sense. If you live longer, then you cost the health system more."
In a paper published online Monday in the Public Library of Science Medicine journal, Dutch researchers found that the health costs of thin and healthy people in adulthood are more expensive than those of either fat people or smokers.
Van Baal and colleagues created a model to simulate lifetime health costs for three groups of 1,000 people: the "healthy-living" group (thin and non-smoking), obese people, and smokers. The model relied on "cost of illness" data and disease prevalence in the Netherlands in 2003.
The researchers found that from age 20 to 56, obese people racked up the most expensive health costs. But because both the smokers and the obese people died sooner than the healthy group, it cost less to treat them in the long run.
On average, healthy people lived 84 years. Smokers lived about 77 years, and obese people lived about 80 years. Smokers and obese people tended to have more heart disease than the healthy people.
Cancer incidence, except for lung cancer, was the same in all three groups. Obese people had the most diabetes, and healthy people had the most strokes. Ultimately, the thin and healthy group cost the most, about $417,000, from age 20 on.
The cost of care for obese people was $371,000, and for smokers, about $326,000.
The results counter the common perception that preventing obesity will save health systems worldwide millions of dollars.
"This throws a bucket of cold water onto the idea that obesity is going to cost trillions of dollars," said Patrick Basham, a professor of health politics at Johns Hopkins University who was unconnected to the study. He said that government projections about obesity costs are frequently based on guesswork, political agendas, and changing science.
"If we're going to worry about the future of obesity, we should stop worrying about its financial impact," he said.
Obesity experts said that fighting the epidemic is about more than just saving money.
"The benefits of obesity prevention may not be seen immediately in terms of cost savings in tomorrow's budget, but there are long-term gains," said Neville Rigby, spokesman for the International Association for the Study of Obesity. "These are often immeasurable when it comes to people living longer and healthier lives."
Van Baal described the paper as "a book-keeping exercise," and said that governments should recognize that successful smoking and obesity prevention programs mean that people will have a higher chance of dying of something more expensive later in life.
"Lung cancer is a cheap disease to treat because people don't survive very long," van Baal said. "But if they are old enough to get Alzheimer's one day, they may survive longer and cost more."
The study, paid for by the Dutch Ministry of Health, Welfare and Sports, did not take into account other potential costs of obesity and smoking, such as lost economic productivity or social costs.
"We are not recommending that governments stop trying to prevent obesity," van Baal said. "But they should do it for the right reasons."
On the Net:
PLoS: http://medicine.plosjournals.org
By MARIA CHENG – 1 day ago
LONDON (AP) — Preventing obesity and smoking can save lives, but it doesn't save money, researchers reported Monday. It costs more to care for healthy people who live years longer, according to a Dutch study that counters the common perception that preventing obesity would save governments millions of dollars.
"It was a small surprise," said Pieter van Baal, an economist at the Netherlands' National Institute for Public Health and the Environment, who led the study. "But it also makes sense. If you live longer, then you cost the health system more."
In a paper published online Monday in the Public Library of Science Medicine journal, Dutch researchers found that the health costs of thin and healthy people in adulthood are more expensive than those of either fat people or smokers.
Van Baal and colleagues created a model to simulate lifetime health costs for three groups of 1,000 people: the "healthy-living" group (thin and non-smoking), obese people, and smokers. The model relied on "cost of illness" data and disease prevalence in the Netherlands in 2003.
The researchers found that from age 20 to 56, obese people racked up the most expensive health costs. But because both the smokers and the obese people died sooner than the healthy group, it cost less to treat them in the long run.
On average, healthy people lived 84 years. Smokers lived about 77 years, and obese people lived about 80 years. Smokers and obese people tended to have more heart disease than the healthy people.
Cancer incidence, except for lung cancer, was the same in all three groups. Obese people had the most diabetes, and healthy people had the most strokes. Ultimately, the thin and healthy group cost the most, about $417,000, from age 20 on.
The cost of care for obese people was $371,000, and for smokers, about $326,000.
The results counter the common perception that preventing obesity will save health systems worldwide millions of dollars.
"This throws a bucket of cold water onto the idea that obesity is going to cost trillions of dollars," said Patrick Basham, a professor of health politics at Johns Hopkins University who was unconnected to the study. He said that government projections about obesity costs are frequently based on guesswork, political agendas, and changing science.
"If we're going to worry about the future of obesity, we should stop worrying about its financial impact," he said.
Obesity experts said that fighting the epidemic is about more than just saving money.
"The benefits of obesity prevention may not be seen immediately in terms of cost savings in tomorrow's budget, but there are long-term gains," said Neville Rigby, spokesman for the International Association for the Study of Obesity. "These are often immeasurable when it comes to people living longer and healthier lives."
Van Baal described the paper as "a book-keeping exercise," and said that governments should recognize that successful smoking and obesity prevention programs mean that people will have a higher chance of dying of something more expensive later in life.
"Lung cancer is a cheap disease to treat because people don't survive very long," van Baal said. "But if they are old enough to get Alzheimer's one day, they may survive longer and cost more."
The study, paid for by the Dutch Ministry of Health, Welfare and Sports, did not take into account other potential costs of obesity and smoking, such as lost economic productivity or social costs.
"We are not recommending that governments stop trying to prevent obesity," van Baal said. "But they should do it for the right reasons."
On the Net:
PLoS: http://medicine.plosjournals.org
You can choose not pain, more freedom study
Brain training puts big hurt on intense pain: volunteers learn to translate imaging data into neural-control tool .highlight{background-color:yellow;font-weight:normal} Preliminary evidence indicates that people can quell either temporary or chronic physical pain by learning to use their minds to reduce activity in a key brain area.
Brain-imaging technology now enables individuals to use mental exercises to control a neural region that contributes to pain perception, say neuroscientist Sean C. Mackey of Stanford University and his colleagues.
Both healthy volunteers and chronic-pain patients "learned to control their brains A computer's "brains" are its central processing unit. See CPU. and, through that, their pain," Mackey holds. "However, significantly more testing must be done before this can be considered a treatment for chronic pain."
The new findings appear in the Dec. 20 Proceedings of the National Academy of Sciences.
Mackey's team studied 32 healthy volunteers, ages 18 to 37. First, each volunteer reported when an adjustable heat pulse applied to a leg produced pain that he or she rated as 7 out of 10, with 10 being equivalent to "the worst pain imaginable." Brain imaging of participants, using a functional magnetic resonance imaging ( fMRI fMRI abbr. functional magnetic resonance imaging ) scanner, showed that this level of pain was accompanied by pronounced blood flow--a sign of intense neural activity--in an area called the rostral 1. pertaining to or resembling a rostrum; having a rostrum or beak. 2. situated toward a rostrum or toward the beak (oral and nasal region), which may mean superior (in relationships of areas of the spinal cord) or anterior or ventral (in relationships of brain areas). anterior cingulate cingulate /cin·gu·late/ (sing´gu-lat) pertaining to a cingulum.
cin·gu·late (snggy cortex.
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Eight of the volunteers then underwent brain training. Each reclined in an fMRI machine that visually displayed activity changes in the person's rostral anterior cingulate cortex. A virtual flame dimmed as activity fell and brightened as activity surged.
While watching this display for 39 minutes, participants tried various mental strategies both to increase and to decrease their brain activity during brief periods of heat-pulse application. The experimenters suggested tactics such as focusing attention away from the pain.
By the end of the training session, the volunteers had learned to raise or lower activity in the critical brain area, the researchers say. The eight volunteers rated pain much higher during robust anterior cingulate cortex activation than during periods of lesser activity in that region.
No such brain-related pain effects occurred for the remaining 24 participants, who were instructed to change their brain activity when they were outside the fMRI machine or in the machine but receiving no feedback, when they received feedback from brain areas unrelated to pain, or when they viewed someone else's pain-related brain activity.
Next, eight chronic-pain patients completed anterior-cingulate-cortex training. Afterward, each reported much less pain--often less than half as much as usual--while he or she mentally quelled the region's activity.
Another four chronic-pain patients used physiological feedback--so-called biofeedback alpha biofeedback presentation of continuous information on the state of the brain-wave pattern, to assist in purposeful increase in the percentage of alpha activity and thus a state of relaxation and peaceful wakefulness.
bi·o·feed·back (b--to learn to control their heart rate, skin conductance airway conductance the reciprocal of airway resistance; the airflow divided by the mouth-to-alveoli pressure difference.
con·duc·tance (kn-dk, and breathing. None succeeded in lessening pain.
Neuroscientist Gary H. Duncan of the University of Montreal calls the new study "a landmark contribution of brain imaging to pain research." It demonstrates that self-controlself-control n. Control of one's emotions, desires, or actions by one's own will.
..... Click the link for more information. over activity in a specific brain region is possible, paving the way for explorations of neural function far beyond the treatment of chronic pain, he says
Brain-imaging technology now enables individuals to use mental exercises to control a neural region that contributes to pain perception, say neuroscientist Sean C. Mackey of Stanford University and his colleagues.
Both healthy volunteers and chronic-pain patients "learned to control their brains A computer's "brains" are its central processing unit. See CPU. and, through that, their pain," Mackey holds. "However, significantly more testing must be done before this can be considered a treatment for chronic pain."
The new findings appear in the Dec. 20 Proceedings of the National Academy of Sciences.
Mackey's team studied 32 healthy volunteers, ages 18 to 37. First, each volunteer reported when an adjustable heat pulse applied to a leg produced pain that he or she rated as 7 out of 10, with 10 being equivalent to "the worst pain imaginable." Brain imaging of participants, using a functional magnetic resonance imaging ( fMRI fMRI abbr. functional magnetic resonance imaging ) scanner, showed that this level of pain was accompanied by pronounced blood flow--a sign of intense neural activity--in an area called the rostral 1. pertaining to or resembling a rostrum; having a rostrum or beak. 2. situated toward a rostrum or toward the beak (oral and nasal region), which may mean superior (in relationships of areas of the spinal cord) or anterior or ventral (in relationships of brain areas). anterior cingulate cingulate /cin·gu·late/ (sing´gu-lat) pertaining to a cingulum.
cin·gu·late (snggy cortex.
write_ads(2,1)
Eight of the volunteers then underwent brain training. Each reclined in an fMRI machine that visually displayed activity changes in the person's rostral anterior cingulate cortex. A virtual flame dimmed as activity fell and brightened as activity surged.
While watching this display for 39 minutes, participants tried various mental strategies both to increase and to decrease their brain activity during brief periods of heat-pulse application. The experimenters suggested tactics such as focusing attention away from the pain.
By the end of the training session, the volunteers had learned to raise or lower activity in the critical brain area, the researchers say. The eight volunteers rated pain much higher during robust anterior cingulate cortex activation than during periods of lesser activity in that region.
No such brain-related pain effects occurred for the remaining 24 participants, who were instructed to change their brain activity when they were outside the fMRI machine or in the machine but receiving no feedback, when they received feedback from brain areas unrelated to pain, or when they viewed someone else's pain-related brain activity.
Next, eight chronic-pain patients completed anterior-cingulate-cortex training. Afterward, each reported much less pain--often less than half as much as usual--while he or she mentally quelled the region's activity.
Another four chronic-pain patients used physiological feedback--so-called biofeedback alpha biofeedback presentation of continuous information on the state of the brain-wave pattern, to assist in purposeful increase in the percentage of alpha activity and thus a state of relaxation and peaceful wakefulness.
bi·o·feed·back (b--to learn to control their heart rate, skin conductance airway conductance the reciprocal of airway resistance; the airflow divided by the mouth-to-alveoli pressure difference.
con·duc·tance (kn-dk, and breathing. None succeeded in lessening pain.
Neuroscientist Gary H. Duncan of the University of Montreal calls the new study "a landmark contribution of brain imaging to pain research." It demonstrates that self-controlself-control n. Control of one's emotions, desires, or actions by one's own will.
..... Click the link for more information. over activity in a specific brain region is possible, paving the way for explorations of neural function far beyond the treatment of chronic pain, he says
effect of exercise on primary prevention of cvd
A systematic review of the evidence on the effects of physical activity found that people who exercise (those who undertake moderate levels of activity daily or almost daily, e.g., walking) typically experience 30%–50% reductions in relative risk of coronary heart disease compared with people who are sedentary after adjustment for other risk factors [1]. Moderate-to-high levels of physical activity are associated with reduced risk of coronary heart disease and stroke. The absolute risk of sudden death after strenuous activity is small (it is greatest in people who are usually sedentary
References
Foster C, Murphy M, Nicholas JJ, Pignone M Bazian Ltd (2005) Primary prevention. Clin Evid 14:1–5.
References
Foster C, Murphy M, Nicholas JJ, Pignone M Bazian Ltd (2005) Primary prevention. Clin Evid 14:1–5.
The Women's Health Initiative Randomized Controlled Dietary Modification Trial 2006 feb6 JAMA
Low-Fat Dietary Pattern and Risk of Cardiovascular Disease
The Women's Health Initiative Randomized Controlled Dietary Modification Trial
JAMA. 2006;295:655-666.
Context Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.
Objective To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.
Design, Setting, and Participants Randomized controlled trial of 48 835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19 541 [40%]) or comparison group (29 294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.
Intervention Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.
Main Outcome Measures Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).
Results By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.
Conclusions Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.
The Women's Health Initiative Randomized Controlled Dietary Modification Trial
JAMA. 2006;295:655-666.
Context Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.
Objective To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.
Design, Setting, and Participants Randomized controlled trial of 48 835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial. Women were randomly assigned to an intervention (19 541 [40%]) or comparison group (29 294 [60%]) in a free-living setting. Study enrollment occurred between 1993 and 1998 in 40 US clinical centers; mean follow-up in this analysis was 8.1 years.
Intervention Intensive behavior modification in group and individual sessions designed to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d. The comparison group received diet-related education materials.
Main Outcome Measures Fatal and nonfatal coronary heart disease (CHD), fatal and nonfatal stroke, and CVD (composite of CHD and stroke).
Results By year 6, mean fat intake decreased by 8.2% of energy intake in the intervention vs the comparison group, with small decreases in saturated (2.9%), monounsaturated (3.3%), and polyunsaturated (1.5%) fat; increases occurred in intakes of vegetables/fruits (1.1 servings/d) and grains (0.5 serving/d). Low-density lipoprotein cholesterol levels, diastolic blood pressure, and factor VIIc levels were significantly reduced by 3.55 mg/dL, 0.31 mm Hg, and 4.29%, respectively; levels of high-density lipoprotein cholesterol, triglycerides, glucose, and insulin did not significantly differ in the intervention vs comparison groups. The numbers who developed CHD, stroke, and CVD (annualized incidence rates) were 1000 (0.63%), 434 (0.28%), and 1357 (0.86%) in the intervention and 1549 (0.65%), 642 (0.27%), and 2088 (0.88%) in the comparison group. The diet had no significant effects on incidence of CHD (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.90-1.06), stroke (HR, 1.02; 95% CI, 0.90-1.15), or CVD (HR, 0.98; 95% CI, 0.92-1.05). Excluding participants with baseline CVD (3.4%), the HRs (95% CIs) for CHD and stroke were 0.94 (0.86-1.02) and 1.02 (0.90-1.17), respectively. Trends toward greater reductions in CHD risk were observed in those with lower intakes of saturated fat or trans fat or higher intakes of vegetables/fruits.
Conclusions Over a mean of 8.1 years, a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused diet and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.
Eades sums up statin studies
"...In men under 65 with no known heart disease but with risk factors, i.e. LDL of 130 mg/dL or greater, the studies cited showed no difference in all cause mortality. For those men under 65 who had very high LDL levels, the evidence showed that these men might have a slight benefit from taking a statin, but nothing to write home about.
In women who are under 65 there is virtually no evidence that statins do squat. In fact, the report doesn’t even produce evidence that cholesterol lowering does anything for women. The report states that it bases its rationale for treatment of women on an extrapolation of data from men.
In men and women over 65 the studies cited show no evidence that cholesterol lowering brings about any significant decrease in risk for heart disease.
Men of all ages with diagnosed heart disease were the only group that the studies used in this report show receive an actual benefit from taking statins. And even that is slight.
Women who have heart disease and who take statins have a reduced death rate from heart disease but no decrease in all-cause mortality..."
In women who are under 65 there is virtually no evidence that statins do squat. In fact, the report doesn’t even produce evidence that cholesterol lowering does anything for women. The report states that it bases its rationale for treatment of women on an extrapolation of data from men.
In men and women over 65 the studies cited show no evidence that cholesterol lowering brings about any significant decrease in risk for heart disease.
Men of all ages with diagnosed heart disease were the only group that the studies used in this report show receive an actual benefit from taking statins. And even that is slight.
Women who have heart disease and who take statins have a reduced death rate from heart disease but no decrease in all-cause mortality..."
observational study shows fruits/veggies lower cvd
In their systematic review of the evidence on the effects of eating more fruit and vegetables for primary prevention of cardiovascular disease, Foster and colleagues found no RCTs [1]. They found three systematic reviews of observational cohort studies, all of which found a protective effect against ischemic heart disease.
References
Foster C, Murphy M, Nicholas JJ, Pignone M Bazian Ltd (2005) Primary prevention. Clin Evid 14:1–5.
References
Foster C, Murphy M, Nicholas JJ, Pignone M Bazian Ltd (2005) Primary prevention. Clin Evid 14:1–5.
vitamin e/beta carotene may increase cvd
A systematic review of antioxidants for primary prevention of cardiovascular disease identified four RCTs of vitamin E; the review found no benefits for vitamin E [1). One of the RCTs identified in the review found that vitamin E may increase death from subarachnoid hemorrhage [2). The review also identified six RCTs of beta-carotene; the review found no benefit for beta-carotene. Pooled analysis of four of these six RCTs found that beta-carotene may increase cv mortality
References
Asplund K (2002) Antioxidant vitamins in the prevention of cardiovascular disease: A systematic review. J Intern Med 251:372–392.
Lepp�l� JM, Virtamo J, Fogelholm R, Huttunen JK, Albanes D, et al. (2000) Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arterioscler Thromb Vasc Biol 20:230–235.
Egger M, Schneider M, Davey Smith G (1998) Spurious precision? Meta-analysis of observational studies. BMJ 316:140–144.
Doering WV (1996) Antioxidant vitamins, cancer, and cardiovascular disease. N Engl J Med 335:1065.
Pietrzik K (1996) Antioxidant vitamins, cancer, and cardiovascular disease. N Engl J Med 335:1065–1066.
References
Asplund K (2002) Antioxidant vitamins in the prevention of cardiovascular disease: A systematic review. J Intern Med 251:372–392.
Lepp�l� JM, Virtamo J, Fogelholm R, Huttunen JK, Albanes D, et al. (2000) Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arterioscler Thromb Vasc Biol 20:230–235.
Egger M, Schneider M, Davey Smith G (1998) Spurious precision? Meta-analysis of observational studies. BMJ 316:140–144.
Doering WV (1996) Antioxidant vitamins, cancer, and cardiovascular disease. N Engl J Med 335:1065.
Pietrzik K (1996) Antioxidant vitamins, cancer, and cardiovascular disease. N Engl J Med 335:1065–1066.
asa lowers MI but increases stroke
The role of aspirin in primary prevention remains uncertain. In a meta-analysis of five RCTs, Foster and colleagues found that aspirin slightly reduced the risk of a serious vascular event (odds ratio, 0.86; 95% CI: 0.80–0.90) and reduced the relative risk of myocardial infarction by about a third (OR, 0.71; 95% CI: 0.60–0.80], but had an uncertain effect on stroke (OR, 1.05; 95% CI: 0.90–1.20) [1]. The meta-analysis found that there were 0.1 excess intracranial bleeds per 1,000 patients treated per year with aspirin, and 0.7 major extracranial bleeds per 1,000 patients treated per year with aspirin. The authors found “insufficient evidence from RCTs to identify which individuals would benefit overall and which would be harmed by regular treatment with aspirin, although those at high and intermediate rather than low risk would be more likely to gain benefit.”
ukpds
UKPDS 38:
To determine whether tight control of blood pressure prevents macrovascular & microvascular complications in patients with type 2
diabetes. Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an
angiotensin converting enzyme inhibitor captopril or a beta blocker atenolol as main treatment) with less tight control aiming at a blood pressure of
<180/105 mm Hg. 20 hospital based clinics in England, Scotland, & Northern Ireland. 1148 hypertensive patients with type 2 diabetes (mean age 56,
mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure & 390 to less tight control with a median
follow up of 8.4 years. Predefined clinical end points, fatal & non-fatal, related to diabetes, deaths related to diabetes, & all cause mortality. Surrogate
measures of microvascular disease included urinary albumin excretion & retinal photography. Mean blood pressure during follow up was significantly
reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg)
(P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related
end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%)
(P=0.013), & 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There
was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34%
reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) & a 47%
reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart.
After 9 years of follow up 29% of patients in the group assigned to tight control required 3 or more treatments to lower blood pressure to achieve target
blood pressures.
CONCLUSIONS : Tight blood pressure control in patients with hypertension & type 2 diabetes achieves a clinically important
reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy & deterioration in visual acuity
To determine whether tight control of blood pressure prevents macrovascular & microvascular complications in patients with type 2
diabetes. Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an
angiotensin converting enzyme inhibitor captopril or a beta blocker atenolol as main treatment) with less tight control aiming at a blood pressure of
<180/105 mm Hg. 20 hospital based clinics in England, Scotland, & Northern Ireland. 1148 hypertensive patients with type 2 diabetes (mean age 56,
mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure & 390 to less tight control with a median
follow up of 8.4 years. Predefined clinical end points, fatal & non-fatal, related to diabetes, deaths related to diabetes, & all cause mortality. Surrogate
measures of microvascular disease included urinary albumin excretion & retinal photography. Mean blood pressure during follow up was significantly
reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg)
(P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related
end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%)
(P=0.013), & 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There
was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34%
reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) & a 47%
reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart.
After 9 years of follow up 29% of patients in the group assigned to tight control required 3 or more treatments to lower blood pressure to achieve target
blood pressures.
CONCLUSIONS : Tight blood pressure control in patients with hypertension & type 2 diabetes achieves a clinically important
reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy & deterioration in visual acuity
framingham study wrt diet snd cholesterol
The project was undertaken between the years 1957-1960 and involved a sample of around 1000 participants who were to be studied over the following 36 months to
test the hypothesis that “The regulation of the level of serum cholesterol and the development of coronary heart disease are related to
1. The caloric balance- sudy showed=>calories per day showed a slight negative association with serum cholesterol (over all age groups) in men but no association in women.
This finding is somewhat puzzling and it is reasonable to inquire if this is related in some way to the level of physical activity. Men in the same physical activity class tend to have higher serum cholesterol levels at lower caloric intake. This finding is contrary to expectation.
2. Level of animal fat intake-study showed=>Paralleling the findings for total calories there is a slight negative association between daily intake of total fat (and also of animal fat) with serum cholesterol level, in men but not in women. This parallel is not surprising given the high correlation between fat intake and total caloric intake. No association between percent of calories from fat and serum cholesterol level was shown;
3. Level of vegetable fat intake- No association...between ratio of plant fat to animal fat intake and serum cholesterol level
4. Level of protein intake-There was a trivial negative correlation between daily protein intake (in grams) and serum cholesterol level
5. Level of cholesterol intake-There is no indication of a relationship between dietary cholesterol and serum cholesterol level. If the intake on animal fat is held constant there is still no relation of cholesterol intake to serum cholesterol level. If (further) a multiple regression is calculated [using animal fat and dietary cholesterol] there is also little suggestion of an association between this pair of variables and serum cholesterol level. IN SUMMARY-
In undertaking the diet study at Framingham the primary interest was, of course, in the relation of diet to the development of coronary heart disease (CHD). It was felt, however, that any such relationship would be an indirect one, diet influencing serum cholesterol level and serum cholesterol level influencing the risk of CHD. However, no relationship could be discerned within the study cohort between food intake and serum cholesterol level.
In the period between the taking of the diet interviews and the end of the 16-year follow-up, 47 cases of de novo CHD developed in the Diet Study group. The means for all the diet variables measured were practically the same for these cases as for the original cohort at risk. There is, in short, no suggestion of any relation between diet and the subsequent development of CHD in the study group… With one exception there was no discernible association between reported diet intake and serum cholesterol level in the Framingham Diet Study Group. The one exception was a weak negative association between caloric intake and serum cholesterol level in men. [As to] coronary heart disease–was it related prospectively to diet. No relationship was found
test the hypothesis that “The regulation of the level of serum cholesterol and the development of coronary heart disease are related to
1. The caloric balance- sudy showed=>calories per day showed a slight negative association with serum cholesterol (over all age groups) in men but no association in women.
This finding is somewhat puzzling and it is reasonable to inquire if this is related in some way to the level of physical activity. Men in the same physical activity class tend to have higher serum cholesterol levels at lower caloric intake. This finding is contrary to expectation.
2. Level of animal fat intake-study showed=>Paralleling the findings for total calories there is a slight negative association between daily intake of total fat (and also of animal fat) with serum cholesterol level, in men but not in women. This parallel is not surprising given the high correlation between fat intake and total caloric intake. No association between percent of calories from fat and serum cholesterol level was shown;
3. Level of vegetable fat intake- No association...between ratio of plant fat to animal fat intake and serum cholesterol level
4. Level of protein intake-There was a trivial negative correlation between daily protein intake (in grams) and serum cholesterol level
5. Level of cholesterol intake-There is no indication of a relationship between dietary cholesterol and serum cholesterol level. If the intake on animal fat is held constant there is still no relation of cholesterol intake to serum cholesterol level. If (further) a multiple regression is calculated [using animal fat and dietary cholesterol] there is also little suggestion of an association between this pair of variables and serum cholesterol level. IN SUMMARY-
In undertaking the diet study at Framingham the primary interest was, of course, in the relation of diet to the development of coronary heart disease (CHD). It was felt, however, that any such relationship would be an indirect one, diet influencing serum cholesterol level and serum cholesterol level influencing the risk of CHD. However, no relationship could be discerned within the study cohort between food intake and serum cholesterol level.
In the period between the taking of the diet interviews and the end of the 16-year follow-up, 47 cases of de novo CHD developed in the Diet Study group. The means for all the diet variables measured were practically the same for these cases as for the original cohort at risk. There is, in short, no suggestion of any relation between diet and the subsequent development of CHD in the study group… With one exception there was no discernible association between reported diet intake and serum cholesterol level in the Framingham Diet Study Group. The one exception was a weak negative association between caloric intake and serum cholesterol level in men. [As to] coronary heart disease–was it related prospectively to diet. No relationship was found
Increased consumption of fruits and vegetables is associated with a "very weak," albeit statistically significant, reduction in overall cancer risk, according to an observational study in the Journal of the National Cancer Institute.
Nearly 480,000 European adults completed food-frequency and lifestyle questionnaires and were followed for roughly 9 years. During that time, 6% were diagnosed with cancer. After adjustment for smoking, alcohol intake, and other confounders, an increase in intake of 200 g/day (roughly 2 servings) of fruits and vegetables was associated with a 4% reduction in overall cancer risk.
An editorialist says the study "strongly confirms" that previous case-control studies were "overly optimistic" and that any link between fruit and vegetable intake and cancer risk "is weak at best." He adds, however, that efforts to increase fruit and vegetable consumption are "still worthwhile," given their beneficial effects on cardiovascular disease.
Nearly 480,000 European adults completed food-frequency and lifestyle questionnaires and were followed for roughly 9 years. During that time, 6% were diagnosed with cancer. After adjustment for smoking, alcohol intake, and other confounders, an increase in intake of 200 g/day (roughly 2 servings) of fruits and vegetables was associated with a 4% reduction in overall cancer risk.
An editorialist says the study "strongly confirms" that previous case-control studies were "overly optimistic" and that any link between fruit and vegetable intake and cancer risk "is weak at best." He adds, however, that efforts to increase fruit and vegetable consumption are "still worthwhile," given their beneficial effects on cardiovascular disease.
Thursday, March 18, 2010
Manitoba steps in to help diabetic - Winnipeg Free Press
Manitoba steps in to help diabetic - Winnipeg Free Press: "'NPH insulin and Lantus are equally effective treatment options for Type 2 diabetes,' the spokesman said. The difference is that NPH must be taken twice a day"
Thursday, March 11, 2010
ontarget arbs and acei
Summary
In high-risk patients with controlled blood pressure but without heart failure, the angiotensin-receptor blocker (ARB) telmisartan is equally effective in reducing cardiovascular risk as the angiotensin-converting enzyme (ACE) inhibitor ramipril and less likely to cause angioedema. Surprisingly, despite a 2 to 3 mmHg additional reduction in blood pressure, combining these drugs in full doses provided no additional clinical benefit — and evidence of some harm — compared with ramipril therapy alone (1). Thus, the ONTARGET [Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial] results, presented at ACC.08 and published simultaneously in the New England Journal of Medicine, confirm that dual blockade with both an ARB and ACE inhibitor produces a greater better blood pressure-lowering effect and more patients with an increase in potassium level of >5.5 mmol/L, yet the combination of telmisartan and ramipril produces more adverse events than either drug alone.
Background
Unlike ACE inhibitors, the ARBs have not been shown to reduce mortality and morbidity in high-risk patients with coronary disease, peripheral vascular disease, cerebrovascular disease, or diabetes. However, in patients with type 2 diabetes, ACE-inhibitor and ARB agents have individually been shown to improve endothelial dysfunction and reduce microalbuminuria. Due to the different mechanisms of action of telmisartan and ramipril, there is the potential for complementary cardiovascular effects independent of their blood pressure-lowering effects. For example, the combination might fully suppress the deleterious effects of angiotensin II and improve endothelial function (2).
ONTARGET is the first long-term prospective trial to investigate the cardioprotective effect of an ACE-inhibitor (ramipril) plus an ARB (telmisartan) in high-risk patients (3). Telmisartan was selected for study because it provides sustained antihypertensive activity effect over the 24-hour period between doses; ramipril was chosen based on the Heart Outcomes Protection Evaluation (HOPE - Ramipril) trial, which showed that ramipril therapy reduced the incidence of cardiovascular events compared to placebo when used in a similar patient population to that planned for ONTARGET (4,5).
Results and Conclusions
The double-blind trial enrolled more than 25,000 patients who were assigned to receive 10 mg ramipril (n = 8,576), 80 mg telmisartan (n = 8,542), or both drugs (n = 8,502) daily. The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.
Compared to the ramipril group, mean blood pressure was lower in both the telmisartan group (a reduction of 0.9/0.6 mmHg) and in the combination therapy group (a reduction of 2.4/1.4 mmHg). At a median follow-up of 56 months, telmisartan was shown to be not inferior to ramipril based on the primary outcome, which had occurred in 1,412 patients in the ramipril group (16.5%) versus 1,423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94-1.09). At the targeted dose of 80 mg once daily, telmisartan preserved 94% (95% CI, 83-105) of the benefit of ramipril 10 mg daily in the HOPE trial.
Also, compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%; p < 0.001) and angioedema (0.1% vs. 0.3%; p = 0.01), but this benefit was partially offset by a higher rate of hypotensive symptoms (2.6% vs. 1.7%; p < 0.001). This is consistent with the slightly better blood-pressure lowering effects seen in the ARB group. Importantly, the rate of syncope was the same in the two groups (0.2%).
In the combination therapy group, the primary outcome results were surprising. Despite a reduction in systolic blood pressure of 2-3 mmHg beyond that seen in the ramipril group — a decrease that should have translated into a risk reduction of 4% to 5% — no significant benefit was seen in the primary composite endpoint, which occurred in 1,386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92-1.07) receiving combination therapy.
However, the two-drug regimen significantly increased the risk of hypotension, syncope, renal dysfunction, and hyperkalemia, with a trend toward an increased risk of renal dysfunction requiring dialysis. These safety results are similar to an analysis of the combined effects of an ARB and an ACE inhibitor (versus an ACE inhibitor alone) in four previous trials (7).
The ONTARGET results are similar to those of the VALIANT study, in which the combination of a full dose of captopril plus half-dose valsartan did not significantly reduce the occurrence of the primary outcome, but did increase hypotension (8). On the other hand, the findings contrast with the CHARM Added study of patients with symptomatic heart failure who had candesartan added to existing therapy including an ACE inhibitor in variable doses (fewer than half of patients received full doses) (9), as well as the Valsartan Heart Failure Trial, in which about 90% of patients had background ACE-inhibitor therapy (again, at variable doses) (10).
In the published results of ONTARGET, the authors admitted that the lack of an additional benefit from greater blood pressuring lowering is puzzling. Perhaps successful treatment with other drugs left little additional clinical benefit possible. Alternatively, they wrote, some harm might be produced with full-dose combination therapy that may offset any gains.
Until additional data become available, the ONTARGET investigators concluded that telmisartan and ramipril are equally effective at reducing cardiovascular risk in patients with vascular disease or high-risk diabetes, even when heart failure is not present. The choice of agent, they said, will depend on the preferences of patients and physicians as well as an individual patient’s susceptibility to specific adverse events.
Guidelines
Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA 2003;289:2560-72.
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