HHAL MEDICAL NEWS MARCH09
Potassium Citrate
to Prevent Recurrent Calcium Stones
Long-term results support treatment with potassium
citrate.
Potassium citrate is used to prevent
recurrent calcium kidney stones.
It works by increasing urinary pH, which enhances urinary citrate excretion; high urinary citrate concentrations increase
the solubility of stone-forming salts. To assess the value of potassium citrate therapy, researchers at Duke University’s Comprehensive Kidney Stone Center conducted a retrospective cohort study of 503 patients who experienced recurrent
kidney stones and who received
potassium citrate therapy. Most patients had some combination of hypocitraturia, low urine volume, hypercalciuria, and gout.
On 24-hour urinary
metabolic profiles at baseline and after at least 6 months of potassium citrate therapy, mean urinary citrate levels rose
from 470 to 700 mg, and mean urinary pH rose from 5.9 to 6.5. During an average treatment duration of 41 months (range, 6–168
months), the stone formation rate dropped from a baseline of 1.89 stones annually to 0.46 stones annually. In a subgroup of
269 patients for whom potassium citrate was the only prescribed medication for stone disease, metabolic and stone outcomes
were similar to those of the overall study population
'Polypill' Lowers Several Measures of Cardiovascular
Risk
A pill containing five generic drugs
reduces measures of risk in people with one risk
factor for heart disease,
according to a phase II study presented at the American College of Cardiology meeting
and published online in Lancet.
The Indian Polycap Study tested a once-daily pill (the "polypill")
containing low-to-moderate doses of thiazide, atenolol, ramipril, simvastatin, and aspirin.
Roughly 2000 people between ages 45 and 80 without cardiovascular disease but with one risk factor (such as hypertension or smoking) underwent randomization. Some received the polypill,
while others received components of the pill.
At 12 weeks, the polypill was noninferior to its individual
components in lowering blood pressure
and heart rate. Measures of cholesterol and antiplatelet activity were slightly in favor of component dosing.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60611-5/fulltext
Rosuvastatin Helps Prevent Venous Thromboembolism
Daily rosuvastatin use in apparently
healthy adults lowers rates of venous thromboembolism (VTE), according to data presented at the American College of Cardiology conference and published online in the New England Journal of Medicine.
In the manufacturer-sponsored JUPITER study, nearly 18,000
apparently healthy men (aged 50 or older) and women (60 or older) were randomized to daily rosuvastatin (20 mg) or placebo.
After a median follow-up of almost 2 years, the rosuvastatin group had significantly lower rates of VTE — either provoked
by such factors as cancer, trauma, or hospitalization, or unprovoked.
The authors write that the effect "appears
to be an independent benefit of statin use, beyond the reduction in the risk of arterial thrombosis." Commenting in Journal Watch Cardiology, Joel Gore says it's premature to
use statins to prevent VTE. He concludes: "A more clinically useful — but not yet studied — question is whether
statins can prevent recurrent VTE."
http://content.nejm.org/cgi/content/full/NEJMoa0900241
Weight Loss, With or Without Orlistat, Improves
NASH(nonalcoholic steatohepatitis)
Stopping Smoking in Early Pregnancy Can Reverse Its Adverse Effects
Featured in
Journal Watch: Excess Risk for Prostate Cancer with Folic Acid Supplementation
Men who took folic acid daily were more likely to develop cancer during 7 years of follow-up.
In a randomized trial
involving women, B vitamins
lowered risk for age-related macular degeneration
but not for cancer or cardiovascular disease
U.K. researchers who analyzed data from 52,700 adults found
those who ate a vegetarian diet
had significantly fewer cancers overall, compared with those who ate meat. They were surprised to find, however, a higher
rate of colorectal cancer among the vegetarians. The study was published in the American Journal of Clinical Nutrition
Both
the CA125 blood test and transvaginal
ultrasound screening strategies are capable of detecting early stage ovarian cancers, with almost half of all cancers detected
in stage I/II. These are the initial findings of the largest randomized
trial of ovarian cancer screening to date, published online first and in the March edition of The Lancet Oncology.
Study: Lowest LDL, BP levels best to prevent heart disease
The best protection against
heart disease
comes with the tightest combined control of blood pressure and LDL cholesterol, according to a study in the Journal of the American
College of Cardiology. For patients
at high risk of heart disease, LDL levels should be below 70
and systolic blood pressure below 120, one study author said
A study in Diabetes Care of almost 3,000 middle-age adults
found those who ate a healthy diet and exercised regularly had less abdominal fat, especially unhealthy layers of deep belly
fat. Researchers also found smokers had more visceral fat than nonsmokers and alcohol intake contributed to higher levels
of deep belly fat in men
Mortality Results from a Randomized Prostate-Cancer Screening Trial
Results In the screening group, rates of compliance were 85%
for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased
from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital
rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was
116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence
interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in
the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The
data at 10 years were 67% complete and consistent with these overall findings.
Conclusions After 7 to 10
years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between
the two study groups. (ClinicalTrials.gov number, NCT00002540
Intensive Glucose Control Harms Critically Ill Patients
Intensive Glucose Control May
Raise ICU Mortality
Aggressive glucose control in critical illness seems to increase mortality, according to a
New England Journal of Medicine study released online.
Investigators in
the NICE-SUGAR trial attempted to define the best glucose target range by randomizing 6100 medical-surgical ICU patients either
to intensive control (81 to 108 mg/dL) or to conventional control (180 mg/dL or less) with use of intravenous insulin. Death
by 90 days (the primary outcome) occurred more often with intensive control than with conventional therapy. Intensive control
also led to more episodes of severe hypoglycemia
(blood glucose, 40 mg/dL or less).
The authors estimate a number needed to harm of 38.
Editorialists point
out that the NICE-SUGAR results "contrast starkly" with earlier trials. Their take on the study's lessons is
that "there is no additional benefit from the lowering of blood glucose levels below the range of approximately 140 to 180."
High Intake
of Red and Processed Meats Linked to Increased Mortality Risk
High intake of red and processed meats is associated with increased risk for death in older adults, while
white meat may have a protective effect, reports Archives of Internal Medicine.
More than a half
million adults aged 50 to 71 completed food-frequency questionnaires and then were followed for 10 years; during that time,
some 48,000 men and 23,000 women died.
After adjustment for confounders including BMI and smoking status, men
and women in the highest quintile of red meat
intake had significantly increased risks for overall mortality, cancer-related deaths, and cardiovascular-disease–related
deaths, relative to those in the lowest quintile. High intake of processed meat was also associated with increased mortality
risks.
Conversely, consumption of white meat (poultry and fish) was associated with significantly decreased
risks for total and cancer-related mortality.
Metformin
Associated with Reduced Macrovascular Disease
Risk
In patients with diabetes treated with insulin, added metformin use is associated
with decreased risk for
macrovascular — but not microvascular — disease, according to an industry-supported
study in Archives of Internal Medicine.
Nearly 400 patients
taking insulin were randomized to added therapy with either metformin or placebo. After 4.3 years' follow-up, there was
no difference between groups in the composite outcome of microvascular disease (e.g., progression of retinopathy, nephropathy,
or neuropathy) and macrovascular disease (e.g., MI, heart failure, stroke, or diabetic
foot).
However, when micro- and macrovascular outcomes were analyzed separately, metformin was associated
with lower risk for macrovascular disease (hazard ratio, 0.61).
The authors say this reduced risk could be partially explained by reduced weight gain in the metformin group. The number needed
to treat to prevent one macrovascular outcome was 16.
Conclusions Metformin, added to insulin in
patients with DM2, improved body weight, glycemic control, and insulin requirements but did not improve
the primary end point. Metformin did, however, reduce the risk of macrovascular disease after a follow-up period
of 4.3 years. These sustained beneficial effects support the policy to continue metformin treatment after
the introduction of insulin in any patient with
DM2, unless contraindicated.
Prevention of Nonvertebral Fractures
With Oral Vitamin D and Dose Dependency: A Meta-analysis of Randomized Controlled Trials
Results
The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral
fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity
for both end points. Including all trials, antifracture efficacy increased significantly with a higher
dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with
a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was
0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures
and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (–29%) and
institutionalized older individuals (–15%), and its effect was independent of additional calcium supplementation.
Conclusion Nonvertebral fracture prevention with vitamin D is dose
dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.
Plasma Vitamin C Level, Fruit and Vegetable Consumption, and the Risk of New-Onset Type 2 Diabetes Mellitus
Conclusions Higher plasma vitamin C level and, to a lesser degree,
fruit and vegetable intake were associated with a substantially decreased risk of diabetes. Our findings highlight
a potentially important public health message on the benefits of a diet rich in fruit and vegetables
for the prevention of diabetes.
Vitamin C Intake and the Risk of Gout in Men
Results During
the 20 years of follow-up, we documented 1317 confirmed incident cases of gout. Compared with men with vitamin
C intake less than 250 mg/d, the multivariate relative risk (RR) of gout was 0.83 (95% confidence interval [CI],
0.71-0.97) for total vitamin C intake of 500 to 999 mg/d, 0.66 (0.52-0.86) for 1000 to 1499 mg/d, and
0.55 (0.38-0.80) for 1500 mg/d or greater (P < .001 for trend). The multivariate RR
per 500-mg increase in total daily vitamin C intake was 0.83 (95% CI, 0.77-0.90). Compared with men who did not
use supplemental vitamin C, the multivariate RR of gout was 0.66 (95% CI, 0.49-0.88) for supplemental
vitamin C intake of 1000 to 1499 mg/d and 0.55 (0.36-0.86) for 1500 mg/d or greater (P < .001
for trend).
Conclusions Higher vitamin C intake is independently associated
with a lower risk of gout. Supplemental vitamin C intake may be beneficial in the prevention of gout.
Treatment-Mediated Change in HDL Cholesterol Levels and CHD Risks
Lowering LDL levels yielded benefit; raising HDL
levels did not.
PCIs No
Better Than Medical Therapy in 'Nonacute' CAD
Percutaneous coronary interventions appear no better than medical therapy for preventing MI or death in patients
with "nonacute" coronary artery
disease, according to a Lancet meta-analysis.
Researchers examined data from 63 randomized,
controlled trials comparing at least two of the following treatments: medical therapy, percutaneous transluminal balloon coronary angioplasty, bare-metal stents,
and drug-eluting stents. More than 25,000 patients with nonacute CAD were included (defined as those with stable and unstable angina, and excluding those
with acute MI).
During a median follow-up of 12 months, neither balloon angioplasty nor stenting proved better than
medical therapy for reducing MI and mortality. (Stenting generally outperformed balloon angioplasty in terms of preventing
coronary artery bypass grafting and revascularization.)
The authors say their results "lend support to present
recommendations to optimise medical therapy as an initial management strategy" for patients with nonacute
Diabetics
and Patients over 65 Show Bigger Survival Benefit from CABG than PCI
Treatment with coronary
artery bypass grafting or percutaneous
coronary intervention provides similar long-term mortality rates in multivessel coronary disease, except in two subgroups, reports a Lancet
study released online.
Researchers examined individual patient data from 10 randomized trials comprising nearly 8000 patients with multivessel
coronary disease. They investigated whether patient characteristics affected long-term mortality rates after CABG or PCI (using
either angioplasty balloons or bare metal stents). The composite outcome of death or MI did not differ between treatment groups. However, patients with diabetes and those aged 65 and older showed a significant survival
advantage with CABG.
Asked to comment, Journal Watch Cardiology's Harlan Krumholz says that "many patients may
prefer the less invasive approach even if the mortality risk is higher — especially older patients — but it is
important that any choice be informed by the evidence
CABG vs. Stenting for Severe Coronary Disease: The SYNTAX Trial
Specific benefits and
harms differ somewhat for the two interventions.
Although coronary-artery bypass grafting (CABG) has been the standard of care for patients with left-main
or three-vessel coronary disease who require revascularization, percutaneous coronary intervention (PCI) with stenting is
also an option in such cases. These two interventions were compared in the SYNTAX trial, which was sponsored by the manufacturer
of the Taxus drug-eluting stent.
Eighteen hundred
patients with previously untreated left-main or three-vessel disease were randomized to CABG or PCI; in each case, either
intervention was deemed feasible by a cardiologist and a surgeon. At 1 year, incidence of the primary composite endpoint (death,
stroke, myocardial infarction, or repeat revascularization) was significantly lower with CABG
than with PCI (12.4% vs. 17.8%). The Table shows differences in outcomes for individual components of the composite endpoint.
Simple Algorithm for Predicting
10-Year Risk for Type 2 Diabetes
A clinical algorithm using "routinely collected data" rather than laboratory measurements can help determine
a patient's 10-year risk for developing type 2 diabetes, researchers report online in BMJ.
The investigators
used electronic medical record
data on some 2.5 million primary care patients in the U.K. to identify independent predictors of incident
diabetes over 10 years. Identified risk factors were then incorporated into a clinical algorithm that was tested in a validation
cohort of roughly 1.2 million adults.
The final algorithm included age, BMI, family history of diabetes, smoking status, treated hypertension, corticosteroid use, presence of cardiovascular
disease, socioeconomic status, and self-reported ethnicity.
Overall, it performed well, with close correspondence between predicted and observed risk. (The risk calculator is available
online; see link.)
The authors conclude that their tool "might be used to identify and proactively
intervene in [high-risk individuals
High and Low BMIs Associated with Increased Mortality Risk
Adults on the lower and higher ends of the BMI scale face increased mortality risk, according to a
study published online by Lancet.
Researchers examined data from 57 prospective studies comprising nearly
900,000 adults who had their BMI measured at baseline. After deaths occurring in the first 5 years' follow-up were excluded,
all-cause mortality was lowest among those with BMIs in the middle range (22.5 to 25 kg/m2).
Above 25, every 5-unit
increase in BMI translated to a:
- 30% increased risk for
all-cause mortality;
- 40% higher risk for death from ischemic heart disease or stroke;
- 60% to 120% increase in renal, hepatic, or diabetic mortality;
- 10% increased risk for cancer-related deaths.
Adults at the lowest end of the BMI scale (below 22.5) were
also at higher risk for death, partly due to smoking-related respiratory disease.
Vitamin K Not Associated with Fewer Bleeding Events in Patients Taking Warfarin
Low-dose vitamin K may not reduce bleeding events in patients receiving
anticoagulant therapy, according to a study in Annals of Internal Medicine.
Some 700 nonbleeding patients who were receiving warfarin
therapy and had elevated international normalized ratios (4.5–10.0) were randomized to oral vitamin K (1.25 mg) or placebo.
Warfarin was stopped the day before randomization and was resumed once the INR reached the target range (2.0–3.5).
The day after the treatment was administered, the average
INR decreased significantly more in the vitamin K group compared with the control group (–2.8 vs. –1.4 INR units).
However, after 90 days' follow-up, the frequency of bleeding events, thromboembolism, or death did not differ significantly
between the groups.
The authors conclude that their results "support the practice of ... simple warfarin therapy withdrawal."
(The latest American College of Chest Physicians guidelines suggest "omitting the next one or two doses" of anticoagulant in patients with
INRs between 5.0 and <9.0 and not at increased bleeding risk — or "alternatively" using oral vitamin K,
particularly in high-risk patients. For those with INRs of 9.0 or greater and no significant bleeding, vitamin K is recommended.)
Using PPIs
with Clopidogrel Associated with Adverse Outcomes After ACS
After acute coronary syndrome, use of a proton
pump inhibitor (PPI) alongside clopidogrel is associated with more frequent rehospitalization or mortality compared
with clopidogrel alone, according to an observational study in JAMA.
Veterans Affairs researchers examined outcomes in some 8200
patients prescribed clopidogrel at discharge after ACS. Nearly two thirds of the patients also received a PPI either at discharge
or during a median 1.5-year follow-up. The primary endpoint, a combination of rehospitalization for ACS or death from any
cause, occurred more often among those taking clopidogrel with a PPI than among those taking clopidogrel alone.
The authors note that previous studies have shown that PPIs
attenuate clopidogrel's antiplatelet effects.
In Journal Watch Cardiology, JoAnne
Foody concludes: "Although [the current] results bear the limitations of all observational studies
... clinicians should consider this potential interaction when they weigh the pros and cons
of prescribing a PPI with clopidogrel for ACS patients."
Never Too
Late to Get Active
Middle-aged
men who increase their physical activity level may see a survival advantage over the long
term, BMJ reports.
Swedish researchers surveyed some 2200 men at age 50 and then followed them for about 35 years, during which four
additional interviews were conducted.
Overall, mortality was lowest among the most active men. In adjusted analyses, men who increased their
activity level from low/moderate to high between the ages of 50 and 60 saw a drop in mortality after 10 years' follow-up,
thereby achieving survival similar to that among men were highly active from the start. (Before 10 years, no survival advantage
was observed.)
The long-term benefit of increased activity was on par with that of quitting smoking during the same period.
Benefits of Urgent Evaluation and Treatment
for TIA and Minor Stroke
Early neurological assessment and treatment is cost-effective and prevents long-term disability.
Do patients with transient ischemic attack (TIA) or minor stroke need urgent specialty
evaluation and treatment? As part of the two-phase, prospective, population-based EXPRESS (Early use of eXisting PREventive
Strategies for Stroke) study, British researchers evaluated the effect of early assessment and treatment on hospital admission,
costs, and disability. In the first phase, 310 patients were referred to a specialty clinic by their primary
care physicians within several days of the acute event, and treatment recommendations were faxed to the primary care
physicians (median time to treatment, 19 days); in the second phase, 281 patients were sent directly to t he specialty clinic
and received treatment the same day.
The
rate of hospital admission for recurrent stroke within 90 days was significantly lower in the second phase than in the first
phase (2% vs. 8%). The number of hospital bed-days for stroke and other cardiovascular conditions declined from 1365 in the
first phase to 427 in the second phase, yielding an average hospital cost savings per patient of £624 (about US$900).
The incidence of fatal or disabling stroke at 6-month follow-up was significantly lower in the second phase than in the first
phase (0.3% vs. 5.1%). The authors conclude that urgent assessment and treatment of patients with minor stroke or TIA
reduces disability and healthcare costs.
Comment: Patients with TIA should be considered to have unstable
angina of the brain and to require urgent attention. Prompt neurological evaluation and treatment not only benefits
individual patients but also results in decreased overall healthcare costs, both in the short term and in the long term (by
reducing severe stroke disability).
Glucose Normalization and Outcomes in Patients
With Acute Myocardial Infarction
Conclusions Glucose normalization after admission is associated with better survival in hyperglycemic patients hospitalized
with acute myocardial infarction whether or not they receive insulin therapy. A strategy of intentional glucose
lowering with insulin therapy needs to be further tested in future randomized controlled trials.
Long-term Benefit of High-Density Lipoprotein Cholesterol–Raising Therapy With Bezafibrate
16-Year Mortality Follow-up of the Bezafibrate
Infarction Prevention Trial
Conclusion Our findings
suggest that HDL-C level–raising therapy with bezafibrate is associated with long-term mortality reduction
that may be related to the degree of HDL-C response to treatment
Weight
Loss for Mild Sleep Apnea
Weight loss
plus lifestyle counseling was effective for most patients with mild sleep apnea.
BP-Lowering Therapy of Substantial
Benefit to Patients with Diabetes and Afib
Patients
with diabetes and atrial fibrillation are at increased risk for adverse outcomes — a
risk that blood pressure-lowering therapy can attenuate — reports the European Heart Journal.
More than 11,000 adults with type
2 diabetes and at least one cardiovascular risk factor were randomized to either perindopril
plus indapamide or placebo; about 8% had afib at baseline.
Among the findings, at 4 years:
- Patients with afib were at greater risk for all-cause mortality (hazard ratio,
1.6), heart failure (HR, 1.7), cerebrovascular events (HR, 1.7), and cardiovascular death
(HR, 1.8), relative to those without afib.
- BP treatment reduced risk for cardiovascular
and all-cause mortality both among patients with and without afib.
- Patients with afib, compared
with hypertensives without afib, saw greater absolute benefits from BP therapy — the number needed to treat for 5 years
to prevent one death was 39 among patients with afib and 84 among those without afib.
Conclusion: Atrial fibrillation is relatively common in type 2 diabetes and is associated with substantially increased
risks of death and cardiovascular events in patients with type 2 diabetes. This arrhythmia identifies
individuals who are likely to obtain greater absolute benefits from blood pressure-lowering treatment. Atrial
fibrillation in diabetic patients should be regarded as a marker of particularly adverse outcome and prompt aggressive
management of all risk factors.
http://eurheartj.oxfordjournals.org/cgi/content/abstract/ehp055
Studies look at obesity's effect on
cognitive decline
Older women who were
obese, had high blood pressure or had low HDL cholesterol
had a 23% higher risk of dementia, a study found. A second report also linked obesity with
cognitive decline in older men but not women. However, a third report suggested being underweight was a risk factor for dementia
among seniors. The studies were published in Neurology.
http://news.yahoo.com/s/hsn/20090311/hl_hsn/obesitydiabetesandheartdiseasemayspeeddementia;_ylt=AtKtsmo7Podnn21YFMmysW_VJRIF
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