http://content.nejm.org/cgi/content/short/362/9/800
Doxycycline Plus Steroids for COPD Exacerbations
Adding
doxycycline to steroids helped resolve symptoms at 10 days in a subgroup of COPD patients.
Daniels JMA et
al. Am J Respir Crit Care Med 2010 Jan 15; 181:150
New York Times Story Questions Prescribing Statins for Healthy People
The New York Times tackles the issue of whether the potential benefits of prescribing
statins to apparently healthy patients outweigh the risks and costs.
A new ad campaign to market rosuvastatin (Crestor) to approximately 6.5 million people without elevated cholesterol
or existing heart problems is expected to begin soon, the article reports. The FDA said in February that the following
people would be eligible: men aged 50 and older and women 60 and older who have one risk factor (e.g., smoking, high
blood pressure) along with elevated high-sensitivity C-reactive protein levels.
The story states that 500 such patients would need to take rosuvastatin for 1 year to prevent one
heart attack. At a cost of $3.50 per pill, it would cost $638,000 to avoid one heart attack.
.
Meanwhile, a recent study in
the Lancet found a small increased risk for diabetes associated with statins
http://www.nytimes.com/2010/03/31/business/31statins.html?pagewanted=print
Cardiovascular Benefits of
Statins vs. Risk for Incident Diabetes
One additional
case of incident diabetes occurred for every 255 patients who received statins for 4 years.
Does statin therapy
raise risk for incident diabetes? When statins were compared with placebo (or usual care), mixed signals have emerged, with
statins seeming to raise diabetes incidence in some trials and to lower it in others.
In a collaborative meta-analysis,
investigators reviewed data from 13 trials in which 90,000 stable nondiabetic patients were randomized to receive a statin
or placebo (or usual care) and were followed for a mean of 4 years. The rate of incident diabetes was slightly but significantly
higher in patients who took statins than in those who received placebo or usual care (4.9% vs. 4.5%; odds ratio, 1.09). In
absolute terms, one additional case of incident diabetes occurred for every 255 patients who received statins for 4 years.
No variations in diabetes risk were noted among different statins. The association of statin use and incident diabetes was
stronger in trials that involved older patients.
INTERPRETATION: Statin therapy is associated with a slightly
increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction
in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease
should not change.
http://www.ncbi.nlm.nih.gov/pubmed/20167359?dopt=Abstract
Endovascular
Repair for Descending Thoracic Aortic Disease?
Data from
nonrandomized trials are encouraging but not conclusive.
Endovascular aortic repair with stent grafts is a less invasive alternative to open surgical repair for
patients with descending thoracic aneurysms. In this systematic review, investigators compared the two treatment
modalities in a meta-analysis of 42 nonrandomized studies that involved almost 6000 patients.
Compared with open repair, endovascular repair was associated with lower 30-day mortality (odds ratio,
0.4), paraplegia (OR, 0.4), cardiac complications (OR, 0.4), and overall complications (OR, 0.2). Mortality at 1
year was not significantly different between procedures, and longer-term data were sparse. Adjustment for potential confounders,
such as patient age at baseline and year of enrollment, did not substantially change the results.
Leg-Length Inequality Is a Risk Factor for Osteoarthritis
Inequality of 1 cm was enough to cause problems.
Harvey WF et al. Ann Intern Med 2010
Mar 2; 152:287
What Age Is Best to Start Screening for Diabetes Among Asymptomatic Patients?
It's best to start screening for type 2 diabetes before middle age and
to repeat screening every few years, according to a Lancet study appearing online.
Using a mathematical model, researchers first simulated a U.S. population
of 325,000 nondiabetic 30-year-olds. Then they tested several screening strategies on each cohort member, measuring cost-effectiveness
against a control strategy of not testing at all until diabetes symptoms or cardiovascular disease developed.
Active screening strategies ranged from starting at age 60 and then repeating
every 3 years to the maximal strategy of starting at 30 with repeats every 6 months.
The best strategy — starting between 30 and 45 with repeats every 3 to 5 years — was the
most cost-effective and enabled a diagnosis of diabetes some 6 years earlier than just waiting for symptoms to develop.
That strategy would prevent seven myocardial infarctions and add 171 quality-adjusted life-years (QALYs) per 1000
people screened over a 50-year span.
Interpretation
In the US population, screening for type 2 diabetes
is cost effective when started between the ages of 30 years and 45 years, with screening repeated every 3—5 years
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62162-0/fulltext
Depression Is an
Inflammatory Disease
A meta-analysis shows higher levels
of two cytokines in depressed patients.
People who are chronically ill often get depressed; depressed people are prone to a variety of medical
illnesses; and pro-inflammatory cytokines can alter mood and promote illness. To determine whether these proteins play a role
in the overlap between depression and inflammation-associated medical disorders, researchers conducted a meta-analysis of
24 case–control studies of basal cytokine levels in a total of 438 unmedicated subjects with major depression and no
comorbid illnesses and 350 medically and psychiatrically healthy controls.
Concentrations of tumor necrosis factor-alpha (TNF- ) and interleukin (IL)-6 were significantly higher
in depressed patients than in controls. The groups showed no significant differences in
other interleukins (IL-1β, IL-4, IL-2, IL-8, or IL-10) or in interferon-gamma.
Comment: IL-6 stimulates differentiation and proliferation of immunoglobulin-secreting B-lymphocytes,
and TNF- stimulates the release of other pro-inflammatory cytokines and inflammatory prostaglandins. In the brain, these
substances inhibit hippocampal neurogenesis; activate the hypothalamic-pituitary-adrenal axis, thus increasing cortisol production;
and indirectly increase production of agonists of the N-methyl-D-aspartate receptor, which promotes apoptosis.
The central actions of these proteins reduce resiliency of the brain and contribute to the hyperactive stress response that
is characteristic of depression, which is further aggravated by loss of hippocampal cells. And, the peripheral actions of these proteins can exacerbate inflammatory diseases, such as diabetes and coronary heart disease.
By the same token, the effects of cytokines in the brain can induce depression in patients with these medical diseases. To
the extent that inflammation is a component of depression and other systemic conditions, anti-inflammatory drugs might prove
helpful (JW Psychiatry Feb 8 2006).
http://www.ncbi.nlm.nih.gov/pubmed/20015486?dopt=Abstract
http://psychiatry.jwatch.org/cgi/content/full/2010/329/1
Vitamin B6 and Colorectal Cancer
A meta-analysis shows lower risk with higher B6 intake or blood levels.
Vitamin B6 and its active form, pyridoxal 5'-phosphate (PLP), have important roles
in DNA synthesis, repair, and methylation and can attenuate cell proliferation and oxidative stress. Therefore, a lower risk
for colorectal cancer with greater intake of B6 or higher blood levels of PLP is biologically plausible.
Researchers examined this relation in a meta-analysis of nine prospective case-control studies of vitamin B6 intake
and four studies of PLP blood levels (total, 7000 participants).
Risk for colorectal cancer in people who had the highest PLP blood levels was lowered by nearly 50% compared with those
who had the lowest levels. Risk in people with the highest B6 intake was about 10% lower than in those with
the lowest intake — a nonsignificant difference. Significant variation existed in the B6 study results,
however; when a large study with the smallest difference between the high- and low-intake groups was omitted, the results
showed a significant 20% lessening of colorectal cancer risk.
CONCLUSION: Vitamin B(6) intake and blood PLP levels were inversely associated with the risk of colorectal
cancer in this meta-analysis.
Larsson SC et al. JAMA 2010 Mar 17; 303:1077
http://www.ncbi.nlm.nih.gov/pubmed/20233826?dopt=Abstract
Light-to-Moderate Drinking Isn't Associated with Excessive Weight Gain
Normal-weight middle-aged-to-older women who were light-to-moderate drinkers were less likely to become
overweight or obese than were their abstinent counterparts.
Normal-weight middle-aged-to-older women who were light-to-moderate drinkers were less likely to become overweight
or obese than were their abstinent counterparts.
Light-to-moderate alcoholic beverage consumption has been associated with both beneficial
(e.g., lower coronary heart disease risk [JW General Medicine Jul 4 2006]) and adverse (e.g., higher breast cancer risk [JW Womens Health Mar 26 2009]) effects in women. But do calories derived from alcohol promote weight gain? Researchers
analyzed data from the Women's Health Study (WHS) of middle-aged or older female healthcare professionals (age range,
38.9–89.0). A total of 19,220 WHS participants (>90% white) had normal self-reported baseline weights (body-mass
index [BMI], 18.5–25.0 kg/m2). Mean daily alcohol and total nutrient intakes were calculated from responses
to periodic food frequency questionnaires. Adjusted analyses considered baseline BMI, smoking status, nonalcohol energy intake,
physical activity, and other lifestyle and dietary factors.
During 12.9 years of follow-up, 41.3% of participants became overweight and 3.8% became obese. Nondrinkers (38% of
participants) were most likely to gain weight. Multivariate adjusted relative risks for overweight and obesity were 0.96,
0.86, 0.70, and 0.73 for increasingly higher quartiles of alcohol intake compared with no alcohol use (P for
trend, <0.001); RRs for obesity were 0.75, 0.43, 0.39, and 0.29 compared with no alcohol use (P for trend,
<0.001). Total caloric intake rose with increasing alcohol use, but caloric intake from other nutrients decreased. Low-to-moderate
drinkers (mean, <1 to 2 drinks daily) had higher physical activity–related energy expenditures than did either women
who drank no alcohol or those who consumed >2 drinks daily; this relation was U-shaped.
http://womens-health.jwatch.org/cgi/content/full/2010/311/1?q=topic_nutrition
Omega-3s for Prodromal Psychosis
A relatively safe intervention yields early positive results.
Amminger GP et al. Arch Gen Psychiatry 2010 Feb 67:146
Hypoglycemia Is Associated with Excess Risk for Death in Critically Ill Patients
Even mild hypoglycemia
was associated with elevated mortality.
In the NICE-SUGAR
trial, intensive insulin therapy raised risks for severe hypoglycemia and 90-day mortality in critically ill patients,
compared with conventional treatment (JW Gen Med Mar 24 2009). In this retrospective study that involved two Australian intensive
care unitsand 4946 patients, investigators assessed the association between hypoglycemia and mortality in critically ill patients.
Overall, 1109 patients (22%) experienced at least one episode of hypoglycemia
(blood glucose level, <81 mg/dL). In-hospital mortality was significantly greater among patients who experienced hypoglycemia
than among normoglycemic patients (37% vs. 20%).Multivariate analysis revealed that illness severity and severity of
hypoglycemia, but not receipt of insulin therapy, were associated independently with elevated mortality.
Comment: Hypoglycemia (either spontaneous or insulin-associated) is
associated with excess mortality in critically ill patients. The reasons for this association are unclear. The authors speculate,
however, that severity of hypoglycemia is associated with severity of illness, that hypoglycemia is a marker of imminent death,
and that hypoglycemia has a true deleterious effect on critically ill patients. This study and prior research clearly indicate
that hypoglycemia should be avoided in critically ill patients.
CONCLUSION: In critically ill patients, an association exists between even mild or
moderate hypoglycemia and mortality. Even after adjustment for insulin therapy or timing of hypoglycemic episode, the more
severe the hypoglycemia, the greater the risk of death.
Egi M et al. Mayo Clin Proc 2010 Mar 85:217
http://www.ncbi.nlm.nih.gov/pubmed/20176928?dopt=Abstract
Another risk factor for cognitive impairment?
Hypercholesterolemia is an early risk factor
for Alzheimer's disease. Low-density lipoprotein (LDL) receptors might be involved in this disorder. Our objective was to determine the risk of mild cognitive impairment in a population of patients with heterozygous
familial hypercholesterolemia, a condition involving LDL receptor dysfunction and lifelong hypercholesterolemia.
Conclusion
Because prior
studies have shown that older patients with sporadic hypercholesterolemia do not show a higher incidence
of mild cognitive impairment, the findings presented suggest that early exposure to elevated cholesterol
or LDL receptor dysfunction may be risk factors for mild cognitive impairment.
http://www.amjmed.com/article/S0002-9343(09)00817-1/fulltext
It's in the genes for never smokers
Genetic variants at 13q31.3 alter the expression
of GPC5 and are associated with susceptibility to lung cancer in never smokers. Downregulation of GPC5 might contribute
to the development of lung cancer in never smokers.
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70042-5/abstract
Study links infertility to prostate cancer in men
A study in Cancer of more than 22,000 California
men found 1.2% of those who were infertile developed prostate cancer in the following decade compared with 0.4%
of those who were not infertile. The risk of being diagnosed with aggressive tumors was 2.6 times higher among infertile men
and the risk for slow-growing tumors was 1.6 times higher, researchers found. http://www.reuters.com/article/idUSTRE62L2VY20100322
Chronic oral anticoagulation: Does it really help?
This study found that, compared with placebo or aspirin, OAC (chronic oral anticoagulation) with or without aspirin
does not reduce mortality or reinfarction. However, it does reduce stroke but is associated
with significantly more major bleeding. We see a need, based on our findings, for revisiting the American College of Cardiology/American
Heart Association guidelines for postinfarction care with respect to OAC.
Conclusion
Notwithstanding these limitations, we concluded that chronic OAC with warfarin does not reduce mortality
or reinfarction after myocardial infarction, regardless of concomitant aspirin administration. There was a significantly higher
rate of bleeding in patients receiving OAC, balanced by a significant protective effect for stroke. Dedicated clinical trials
may be able to identify selected subsets of patients who could still benefit from OAC in the current era. These results do
not exclude the possibility that carefully monitored INR at a moderate intensity may prevent the combination of ischemic events
analyzed separately in this study. We see a need, based on our findings, for revisiting the American College of Cardiology/American
Heart Association guidelines for postinfarction care with respect to OAC.
http://www.amjmed.com/article/S0002-9343(09)00818-3/fulltext
Psoriasis is a risk factor for heart attack, stroke
Psoriasis may raise the risk of heart attack,
stroke and other cardiovascular problems, likely through a shared inflammatory response, Danish researchers reported at the
annual meeting of the American College of Cardiology. Study data showed severe psoriasis raised the risk of a heart attack
by 24%, and having moderate or severe disease increased the odds of a stroke by 45%.
http://www.healthday.com/Article.asp?AID=637001
Heart disease, erectile dysfunction together raise mortality risk
A study in Circulation found men with heart
disease and erectile dysfunction had twice the risk of death from any cause and twice the risk of a heart attack compared
with men who only had heart disease. The researchers said patients with erectile dysfunction should be evaluated by a cardiologist.
http://www.reuters.com/article/idUSTRE62E4SL20100315
Survey finds too few Americans get regular exercise
National Health Interview Survey data from
interviews with 79,000 U.S. adults over three years found 61% drink alcohol, 20% smoke and 40% don't get any regular leisure-time
physical activity. On the upside, 31% do participate in regular physical activity and 58.5% have never smoked cigarettes.
http://usatoday.printthis.clickability.com/pt/cpt?action=cpt&title=U.S.+health+survey:+Too+few+exercise,+too+many+smoke+-+USATODAY.com&expire=&urlID=422835572&fb=Y&url=http://www.usatoday.com/news/health/2010-03-17-healthhabits17_ST_N.htm&partnerID=1660
Don't trick the hunger signal among the elderly
Feeding elderly people that have decreased
appetite a high fat meal that includes oil and butter may increase the satiety signal from
GLP-1 and consequently decrease hunger and decrease calorie intake. Given that protein-energy malnutrition is a common
problem in elderly, eating a high-fat lunch may blunt hunger for dinner.
Conclusion
In healthy elderly people relatively large amounts of fat increase the satiety signal from GLP-1 and
lower the acylated to desacylated ratio of ghrelin, consequently decreasing hunger. This condition may lead to a reduction
in calorie intake.
Journal of the American Medical Directors Association
http://www.jamda.com/article/PIIS152586100900276X/abstract
Family history is key in stroke risk, study finds
A U.S. study in Circulation found that children
of men or women who had a stroke by age 65 had a fourfold increased risk of stroke by that age and double the risk of stroke
at any age. The lead researcher said people with a positive family history of stroke should work to modify risk from other
factors, such as good blood pressure control, exercise and maintaining a healthy weight.
http://www.healthday.com/Article.asp?AID=636799
Study shows mental benefits of exercise and diet
Eating well and getting
regular exercise can improve the mind as well as the body, research indicates. The study
in Hypertension divided participants into a group that changed diet, one that improved diet and exercise, and one that made
no changes, and found a 30% improvement in mental function in the diet-and-exercise group.
http://healthday.com/Article.asp?AID=636763
A new danger in regular analgesic use
These authors found that regular use of aspirin, NSAIDs or acetaminophen increases the risk of hearing loss in men, and the impact
is larger on younger individuals. In addition, for NSAIDs and acetaminophen, the risk increased with longer duration of regular
use.
Conclusions
Regular use
of aspirin, NSAIDs, or acetaminophen increases the risk of hearing loss in men, and the impact is larger on younger individuals.
The American Journal of Medicine
http://www.amjmed.com/article/S0002-9343(09)00795-5/fulltext
Carotid stenting vs. standard surgery in stroke prevention
Completion of long-term follow-up is needed
to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
Periprocedural
risk was lower with endarterectomy, but longer-term risk was similar with either procedure.
Carotid artery
stenting is an alternative to carotid endarterectomy for patients with carotid artery stenosis. But which procedure is safer?
In this meta-analysis of 11 randomized controlled trials that involved 4800 patients (300 asymptomatic), investigators compared
carotid endarterectomy with carotid artery stenting.
Periprocedural (within 30 days) outcomes for the primary
study endpoint (death or stroke) and secondary endpoints are shown in the Table. Intermediate-term (1–4 years postprocedure) risk for death or stroke did not differ between procedures.
http://www.ncbi.nlm.nih.gov/pubmed/20154049?dopt=Abstract
.
The Lancet Neurology
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60239-5/abstract
Low fat, low-carb, Mediterranean diets lower heart risks
Low-fat, low-carbohydrate and Mediterranean
diets all can help to reverse thickening of the artery walls that can lead to heart attack and stroke, Israeli researchers
said. The study in Circulation found that even if weight loss is only moderate, sticking to the diets long-term can reverse
atherosclerosis. HealthDay News
http://www.healthday.com/Article.asp?AID=636488
Bisphosphonates' Link with Atypical Femur Fractures Inconclusive
Femoral-shaft
fractures associated with the use of bisphosphonate drugs are rare, an industry-supported study finds. However, the study's statistical
power was too low to examine the association conclusively.
Researchers reevaluated subtrochanteric and diaphyseal femur fractures from three large clinical trials of
bisphosphonates comprising over 14,000 patients. Although the analysis found increased risks for femoral-shaft fractures,
the risks did not reach statistical significance. In addition, because only 12 such fractures were found, confidence
intervals were very wide.
An editorialist in the New
England Journal of Medicine, which released the study online, says the findings have two clinical implications: first,
that subtrochanteric fractures are "extremely rare"; and second, "the findings also suggest that many more
common and equally devastating hip fractures are prevented by bisphosphonates than are potentially caused by the
drugs."
Conclusions The occurrence of fracture of the subtrochanteric or
diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as
10 years. There was no significant increase in risk associated with bisphosphonate use, but
the study was underpowered for definitive conclusions.
http://content.nejm.org/cgi/content/full/NEJMoa1001086
An Hour of Daily Exercise Helps Ward Off Weight Gain in Middle-Aged Women
Patients may
ask about a widely reported JAMA study suggesting that 1 hour of moderate exercise daily is needed to prevent
weight gain in middle-aged women.
Roughly 34,000 women
(mean age at enrollment, 54) in the Women's Health Study answered questionnaires about their weight and exercise habits
at baseline and periodically over 13 years' follow-up.
After adjusting for reported diet at baseline, researchers found that over any 3-year period, women who exercised <150
minutes weekly or 150 to <420 minutes weekly were, respectively, 11% and 7% more likely to gain 2.3 kg (5 lb.), compared
with women who exercised =420 minutes a week.
The authors
point out that the association was observed only among women with a body-mass index less than 25, noting that "among
heavier women, there was no relation, emphasizing the importance of controlling caloric intake for weight maintenance in this
group."
Conclusions Among women consuming a usual diet, physical activity
was associated with less weight gain only among women whose BMI was lower than 25. Women successful in maintaining normal
weight and gaining fewer than 2.3 kg over 13 years averaged approximately 60 minutes a day of moderate-intensity
activity throughout the study.
http://jama.ama-assn.org/cgi/content/short/303/12/1173
Lenient Heart Rate Control As Effective As Strict Control in Atrial Fibrillation
For patients with atrial fibrillation (AF), lenient heart rate control is as effective as guideline-recommended strict
control, according to a study presented Monday at the American College of Cardiology conference.
Researchers in
the Netherlands randomized some 600 patients with permanent AF to undergo lenient rate control (resting heart rate, <110
beats/min) or strict control (resting rate, <80 beats/min; rate during moderate exercise, <110 beats/min). The primary
outcome was a composite of cardiovascular death, hospitalization for heart failure, stroke, systemic embolism, major bleeding,
and arrhythmic events.
The estimated 3-year incidence of the primary outcome was similar in the two groups (13% with lenient
control and 15% with strict control), as was the incidence of each of the components of the primary endpoint.
An
editorialist in the New England Journal of Medicine points out study limitations but concludes that although lenient
rate control "may make physicians feel uncomfortable, [it] is probably as useful as the current guideline-recommended
target heart rates."
Conclusions In patients with permanent atrial fibrillation, lenient
rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613
[ClinicalTrials.gov] .)
N Engl
J Med 2010 Mar 15;
http://content.nejm.org/cgi/content/full/NEJMoa1001337
http://cardiology.jwatch.org/cgi/content/full/2010/315/1?q=etoc_jwgenmed
The ACCORD Lipid Study: Fenofibrate Doesn't Help
Although triglyceride levels improved
markedly with fenofibrate, incidence of adverse cardiovascular events was not affected.
Interventions that improve lipid profiles do not always improve patient outcomes. A common strategy in
diabetic patients — who often have low HDL and elevated triglyceride levels — is to add fibrate therapy, despite
mixed results in previous studies. In the government-funded ACCORD Lipid Study, researchers evaluated whether adding fenofibrate
to statin therapy prevents adverse cardiovascular events in patients with type 2 diabetes.
More than 5000 diabetic adults (mean age, 62; 31% women; glycosylated hemoglobin, 7.5%; LDL cholesterol,
60–180 mg/dL; HDL cholesterol, <55 mg/dL for women and blacks and <50 mg/dL for all others) were enrolled. All
participants received simvastatin and also were assigned to daily fenofibrate (160 mg) or placebo. Mean follow-up was 4.7
years.
In both groups, mean LDL levels dropped from
100 mg/dL to 80 mg/dL. Mean HDL levels increased from 38.0 mg/dL to 41.2 mg/dL in the fenofibrate group and to 40.5
mg/dL in the placebo group. Median triglyceride levels decreased from about 160 mg/dL to 122 mg/dL in the fenofibrate group
and to 144 mg/dL in the placebo group. The primary endpoint, adverse cardiovascular events, occurred with similar frequency
in the two groups (2.2% vs. 2.4% per year; hazard ratio, 0.92; P=0.32). No subgroup analysis was strongly positive,
although women assigned to fenofibrate had higher adverse event rates than did women assigned to placebo. Fenofibrate recipients
were significantly more likely than placebo recipients to leave the study (2.4% vs. 1.1%) because of a decrease in glomerular
filtration rate.
http://cardiology.jwatch.org/cgi/content/full/2010/314/1?q=topic_lipid
High-Dose Simvastatin May Increase Risk for Muscle Injury, FDAWarns
Patients who
are taking the highest approved dose of the cholesterol-lowering drug simvastatin (Zocor) may face increased risk for muscle
injury compared with those taking lower doses or "possibly" other statins, the FDA warned on Friday.
Reviewing preliminary data from one clinical trial, the agency found that
muscle injury, includingrhabdomyolysis, was more common among patients on the 80-mg dose of simvastatin versus a 20-mg dose
(0.9% vs. 0.02%).
As part of an ongoing safety review
of the drug, the FDA is also examining data from otherclinical trials, observational studies, and adverse event reports.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019766s078lbl.pdf
Rapid Kidney Function Decline and Mortality Risk in Older Adults
Dena E. Rifkin, MD; Michael G.
Shlipak, MD, MPH; Ronit Katz, DPhil; Linda F. Fried, MD, MPH; David Siscovick, MD, MPH;Michel Chonchol, MD; Anne
B. Newman, MD; Mark J. Sarnak, MD, MS
Arch Intern Med. 2008;168(20):2212-2218.
Background Impaired
kidney function is associated with increased mortality risk in older adults. It remains unknown,however, whether
longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality
in older adults.
Methods The Cardiovascular Health Study evaluated
a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities
with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration
rate (eGFR) was estimated using both serum creatinine (eGFRcreat) and cystatin C (eGFRcys)
rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in
eGFR was defined as a loss greater than 3 mL/min/1.73 m2 per year, and cardiovascular and all-cause mortality
were assessed over a mean of 9.9 years of follow-up.
Results Mean
(SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean(SD)
eGFRcreat and eGFRcys were 79 (23) mL/min/1.73 m2 and 79 (19)
mL/min/1.73 m2, respectively. Individuals with rapid decline measured by eGFRcreat (n = 714;
16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence
interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured
by eGFRcys (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53;
95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid
decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function,
age, sex, race, or prevalent coronary heart disease.
Conclusion Rapid
decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older
adults, independent of baseline eGFR and other demographic variables.
Strong Evidence Linking Lp(a) to Coronary Artery Disease
A genetic association study bolsters the case for a causal mechanism.
Clarke R et al. for the PROCARDIS Consortium. N Engl J Med 2009
Dec 24; 361:2518
Does Absence of Coronary Artery Calcification Exclude Obstructive Coronary Artery Disease?
In symptomatic patients, overall sensitivity of a CAC score of 0 for predicting absence
of obstructive CAD was only 45%.
Gottlieb I et al. J Am Coll Cardiol 2010 Feb 16; 55:627
Pneumatic Compression vs. Compression Stockings to Prevent Thrombosis
In a systematic review, pneumatic compression had the edge.
A guideline from the American College of Chest Physicians recommends that mechanical methods be used when high bleeding risk precludes use
of antithrombotic drugs in patients at risk for deep venous thrombosis (DVT). However, the guideline does not take
a position favoring intermittent pneumatic compression (IPC) or graduated compression stockings (GCS).
In this systematic review, researchers examined 10 studies (9 in surgical
patients) in which the two methods were compared. In three randomized trials, DVT incidence was significantly lower with
IPC than with GCS. However, only about 100 patients were enrolled in each trial, and — in two of them — patients
in both groups received antithrombotic drugs in addition to randomized mechanical prophylaxis. The other seven studies showed
no difference between IPC and GCS, but most involved fewer than 100 patients. In the only large study (involving 1500 total
hip arthroplasty patients), assignment of IPC or GCS was not randomized.
http://www.ncbi.nlm.nih.gov/pubmed/20083996?dopt=Abstract
The ACCORD Blood Pressure Study: What Target for High-Risk Diabetic Patients?
Achieving systolic blood pressure levels lower than 140 mm Hg does not prevent adverse cardiovascular
events.
In epidemiological studies, lower blood pressure (BP) is associated with lower cardiovascular risk.
But, in high-risk patients, would achieving blood pressure targets lower than those recommended in guidelines reduce risk
further? Researchers evaluated whether a blood pressure target of <120 mm Hg in patients with type 2 diabetes would lower
risk for adverse cardiovascular events.
A total of 4733 high-risk diabetic patients (mean age, 62; 48% women;
glycosylated hemoglobin, 7.5%; systolic blood pressure [SBP], 130–180 mm Hg) who were taking 3 antihypertensive medications
and had no proteinuria were enrolled. Patients were assigned to intensive BP control (target SBP, <120 mm Hg) or standard
BP control (target SBP, <140 mm Hg). Mean follow-up was 4.7 years. Mean systolic and diastolic BP levels at baseline were
139 mm Hg and 76 mm Hg, respectively. At 1 year, average SBP levels were 119 mm Hg in the intensive-care group and 134 mm
Hg in the standard-care group. The lower BP in the intensive-care group was achieved by prescribing more drugs in every antihypertensive
class; the mean number of medications at 1 year was 3.4 in the intensive group and 2.1 in the standard-care group.
At
5 years, the rate of adverse cardiovascular events was 1.9% per year in the intensive-care group and in 2.1% per year in the
standard-care group (hazard ratio, 0.88; P=0.2). Death rates were similar in the two groups. No secondary analysis
was strongly positive, except that stroke incidence was significantly lower in the intensive-care group than in the standard-care
group (0.32% vs. 0.53%). The intensive-care group had a higher rate of serious adverse events, with more decrements in renal
function and more episodes of syncope, bradycardia, hyperkalemia, and hypotension. Overall, 3.3% of the intensive-care group
had adverse events attributed to the medications, compared with 1.3% of the standard-care group.
http://cardiology.jwatch.org/cgi/content/full/2010/314/2?q=topic_hypertension
Nateglinide,
Valsartan Have Little Effect on Preventing Diabetes or Cardiovascular Events
In patients with impaired glucose tolerance, studies of two drugs — one an insulin secretagogue
and the other an angiotensin receptor blocker — met with little success in delaying diabetes onset and cardiovascular
complications.
The studies, deriving from the randomized NAVIGATOR trial, were designed and conducted by the drugs'
manufacturer. The studies were presented Sunday at the American College of Cardiology conference.
In
a 2 x 2 factorial design, some 9300 patients with impaired glucose tolerance and high cardiovascular risk received valsartan,
nateglinide, or a corresponding placebo combination. The primary outcomes were the development of diabetes and a composite
of cardiovascular events.
After roughly 6 years' follow-up, nateglinide, as compared with placebo, did
not reduce the incidence of diabetes or cardiovascular complications. Valsartan modestly lowered the incidence of diabetes,
but not cardiovascular events.
An editorialist writes that "for now we should steer away from these two
drugs and use effective lifestyle interventions and, in selected persons, metformin."
Hypothesis Links Blood Pressure Variability to
Stroke Risk in Hypertension
Stroke risks in hypertension seem more related to the variability of a patient's
systolic pressure than to mean pressure, according to studies in the Lancet and Lancet Neurology.
One
study, examining stroke risk in cohorts comprising some 25,000 hypertensives, found heightened risk in those with greater
visit-to-visit variability in systolic pressure. Patients on the calcium-channel blocker
amlodipine showed less pressure variability (and lower stroke risk) than those on the beta-blocker atenolol.
Another
study examined risk in relation to pressure variability among patients who had a previous transient ischemic attack. It found
variability and maximum systolic pressure to be strong predictors of risk.
A meta-analysis of drug-class effects
found lower variability with calcium-channel blockers and non-loop diuretics, and increased variability with ACE inhibitors,
angiotensin-receptor blockers, and beta blockers.
A Lancet Neurology commentator calls the results "compelling,"
and says they "might set the foundation for a major change in our practice."
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(10)70066-1/abstract
Does Aspirin Extend Breast Cancer Survival?
Aspirin use was associated with lower risk for distant recurrence and breast cancer-related death
Preventing Sudden Cardiac Death in Athletes
Screening theoretically is cost-effective, but
many practical barriers remain.
CONCLUSION: Adding ECG to medical history and
physical examination improves the overall sensitivity of preparticipation cardiovascular screening in athletes. However,
this strategy is associated with an increased rate of false-positive results when current ECG interpretation criteria are
used.
Baggish AL et al. Ann Intern Med 2010 Mar 2; 152:269
Maron
BJ. Ann Intern Med 2010 Mar 2; 152:324
http://www.ncbi.nlm.nih.gov/pubmed/20194233?dopt=Abstract
Providing Coronary Risk Information to Patients
Primary Prevention of Cardiovascular Events with Aspirin
No benefit was observed in a group at high risk for vascular disease.
Fowkes FGR et
al. JAMA 2010 Mar 3; 303:841
Berger JS. JAMA 2010 Mar 3; 303:880
Testosterone Supplements for Frail Aging Men?
In a short-term
randomized trial, only a few outcomes improved.
Srinivas-Shankar U et al. J Clin Endocrinol Metab
2010 Feb 95:639
Middle-Aged Women Who Drink
Alcohol May Gain Less Weight Than Nondrinkers
Women
who drink light-to-moderate amounts of alcohol may gain less weight than nondrinkers as they age, reports the Archives
of Internal Medicine.
Some 19,000 normal-weight, middle-aged female health professionals answered alcohol
and food-frequency questionnaires and then were followed for an average of 13 years. During that time, 41% became overweight
or obese.
After adjustment for factors including age, non-alcohol energy intake, and physical activity, women
who drank roughly 0.5 to 2 drinks per day were significantly less likely to become overweight or obese during follow-up, compared
with those who abstained from drinking.
The authors write that alcohol consumption might result in a net energy
loss in women (possibly explained by metabolic changes or less caloric intake from food). However, they stress the importance
of "evaluating both adverse and beneficial effects of the drinking behavior in a broad context" before making recommendations
on alcohol use.
Conclusion Compared with nondrinkers, initially normal-weight women who consumed a light
to moderate amount of alcohol gained less weight and had a lower risk of becoming overweight and/or obese
during 12.9 years of follow-up.
http://archinte.ama-assn.org/cgi/content/short/170/5/453?home
The Metabolic
Syndrome, Its Component Risk Factors, and Progression of Coronary Atherosclerosis
Ozgur Bayturan, MD; E. Murat Tuzcu, MD; Andrea Lavoie, MD; Tingfei Hu, MS; Kathy Wolski, MPH; Paul
Schoenhagen, MD; Samir Kapadia, MD; Steven E. Nissen, MD; Stephen J. Nicholls, MBBS, PhD
Arch Intern Med.
2010;170(5):478-484.
Background The mechanism that confers adverse cardiovascular prognosis in patients with
the metabolic syndrome (MetS) remains unclear. We sought to investigate the association of MetS and its
component risk factors with progression of coronary atherosclerosis.
Methods We performed a systematic review
of 3459 patients who participated in 7 clinical trials that monitored coronary atheroma progression
with intravascular ultrasonography. Patients with or without MetS were compared with regard to clinical characteristics,
coronary atheroma burden at baseline, and change on serial evaluation. Relationships between plaque progression
(5% increase in percent atheroma volume [PAV]), MetS, and its component risk factors were investigated.
Results
The metabolic syndrome was highly prevalent and was associated with greater progression of PAV (+0.51% ±
0.23% vs +0.23% ± 0.24%; P = .003). Multivariable analysis showed that MetS was associated
with a greater likelihood of undergoing progression of PAV (adjusted odds ratio [OR], 1.25; 95% confidence
interval [CI], 1.05-1.48; P = .01). When the individual components were used in the model instead
of MetS, hypertriglyceridemia (OR, 1.26; 95% CI, 1.06-1.49; P = .008) and a body mass index of 30
or higher (1.18, 1.00-1.40; P = .05) predicted progression of PAV. However, after adjusting
for its individual components, MetS was no longer an independent predictor (OR, 1.04; 95% CI, 0.79-1.37; P
= .79).
Conclusion Although accelerated disease progression is observed in the setting of MetS,
this is owing to the presence of individual component risk factors rather than to the presence of the
syndrome itself.
http://archinte.ama-assn.org/cgi/content/abstract/170/5/478?ct
Aspirin Fails to Prevent Cardiovascular Events in Patients with a Low Ankle-Brachial Index
Giving aspirin to patients at increased risk for cardiovascular disease (on
the basis of low ankle-brachial scores) apparently does not lower their risk, JAMA reports.
Researchers randomized
some 3400 patients without clinically evident cardiovascular disease, but with ankle-brachial indexes of 0.95 or less, to
either aspirin (100 mg per day) or placebo. Median age at entry was 62.
The primary endpoint was a composite of
coronary events, stroke, or the need for revascularization. After roughly 8 years of follow-up, event rates did not differ
between the groups. Rates of secondary endpoints (including angina, intermittent claudication, or transient ischemic attack)
also did not differ.
An editorialist writes that, despite aspirin's effectiveness in secondary prevention, "the clinical benefits of aspirin therapy for patients with peripheral artery disease remain unproven."
More Data on Fracture Risk with Thiazolidinediones
Risk was particularly elevated among older women.
A growing body of evidence has linked
thiazolidinediones (TZDs; i.e., rosiglitazone and pioglitazone) to fracture risk. This adverse effect is plausible: Receptors
for TZDs are expressed in bone, and rosiglitazone therapy affects bone turnover and reduces bone-mineral density (JW Gen Med Apr 24 2007).
The latest contribution to this literature is a retrospective study of 19,000 patients with type 2
diabetes who received oral antidiabetic drugs while enrolled in a Michigan health maintenance organization; 24% of these patients
were prescribed TZDs. In multivariate analyses that were adjusted for numerous potentially confounding variables, women who
used TZDs had significantly elevated risk for fractures compared with nonusers (hazard ratio, 1.57). The excess risk emerged
after 1 year of treatment and was especially striking in older women (age, >65; HR, 1.72). Elevated fracture risk was not
observed in men.
Conclusions: TZD use was associated with an increased risk for fractures
in women, particularly at ages above 65 yr. Clinicians should be aware of this association when considering TZD therapy
so as to appropriately manage and counsel their patients.
http://www.ncbi.nlm.nih.gov/pubmed/20061432?dopt=Abstract
