HHAL MEDICAL NEWS JULY2010

Calcium Supplements Reportedly Raise Risk for Myocardial Infarction

Patients on calcium supplements show a modest increase in risk for myocardial infarction, according to a BMJ meta-analysis.

Investigators gathered data on some 12,000 participants in randomized controlled trials using calcium supplements without vitamin D. Subjects on calcium showed a roughly 30% increase in risk for MI and nonsignificant increases for stroke, death, and the composite outcome of MI, stroke, or sudden death.

The authors propose that one mechanism for the effect could be the danger of increased vessel calcification. They estimate that although treating 1000 people for 5 years would prevent 26 fractures, it would also lead to 14 MIs, 10 strokes, and 13 deaths.

An editorial concludes: "Patients with osteoporosis should generally not be treated with calcium supplements, either alone or combined with vitamin D, unless they are also receiving an effective treatment for osteoporosis."

Conclusions Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.

http://www.bmj.com/cgi/content/full/341/jul29_1/c3691

European Study Suggests Prostate Cancer Screening Lowers Mortality

Screening for prostate cancer reduces mortality from the disease by about half, but at the cost of overdiagnosis, according to a Lancet Oncology study.

Some 20,000 residents of Göteborg, Sweden, were randomized either to be invited for prostate-specific antigen (PSA) testing at 2-year intervals or not to be invited. Those with PSA levelsabove a prespecified threshold were offered further work-up. After a median 14-year follow-up, the risk for prostate cancer death was 0.5% among those screened and 0.9% among the controls.

The authors calculate a number needed to screen of 293 to prevent one death.

An editorialist concludes that the study is "probably not generalizable" to the U.S. population; rather, the results are more likely generalizable to populations that have not undergone extensive PSA testing.

Interpretation

This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs.

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70146-7/abstract

Obesity Raises Risk for Diabetes

Weight gain after age 50, just like earlier in life, raises risk.

Obesity and excess body fat are risk factors for developing diabetes, but in mid- and late-life the association of various measures of adiposity with diabetes is less clear. A population-based prospective cohort study was used to follow about 4000 older people (age,  65 at enrollment) for a median of 12 years; 339 incident cases of diabetes were identified.

Risk for developing diabetes was roughly three- to fourfold higher for people in the highest quintile of adiposity than for those in the lowest. Risk associated with measures of body composition included body-mass index (BMI) at baseline (hazard ratio, 4.3 for the highest quintile), waist circumference (HR, 4.2), fat mass (HR, 4.0), waist-height ratio (HR, 3.8), BMI at age 50 (by self-recall; HR, 3.0), and waist-hip ratio (HR, 2.4). Risk conferred by adiposity in the oldest individuals (age,  75) was roughly half that in younger individuals (age range, 65–74). Compared with people who had gained no weight, those who had gained the most weight from age 50 to baseline or from baseline to the final follow-up assessment had two- to threefold higher risk for developing diabetes.

Comment: That almost any measure of obesity or adiposity is associated with risk for developing diabetes is not surprising, even in older patients. What is more interesting is that weight gain after age 50, compared with no weight gain, was associated with higher risk. Keep in mind, however, that overweight or mild obesity is not necessarily associated with higher mortality in older populations (JW Gen Med Jan 19 2010).

http://www.ncbi.nlm.nih.gov/pubmed/20571017?dopt=Abstract

Naltrexone-Bupropion Plus Lifestyle Changes Better Than Lifestyle Changes Alone for Weight Loss

Adding a naltrexone-bupropion pill to lifestyle changes leads to greater weight loss than lifestyle changes alone, according to a manufacturer-conducted, phase III study in the Lancet.

Researchers randomized some 1700 overweight or obese adults to daily treatment with either sustained-release naltrexone (16 or 32 mg) plus bupiopion (360 mg), or placebo. All participants were also instructed to consume fewer calories and exercise more.

At 56 weeks, mean weight loss was greater with naltrexone-bupropion (5–6% of body weight) than with placebo (1%). Combination therapy also improved secondary outcomes, including waist circumference and triglycerides. Serious adverse events did not differ between active treatment and placebo.

A commentator notes that reductions in blood pressure and LDL cholesterol, normally seen with weight loss, were not observed in this trial. He calls for more data to "get a better overall assessment of cardiovascular risk of this otherwise promising combination therapy."

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60888-4/fulltext

Tinnitus: Who's got it and why?
The prevalence of frequent tinnitus is highest among older adults, non-Hispanic whites, former smokers, and adults with hypertension, hearing impairment, loud noise exposure, or generalized anxiety disorder.Prospective studies of risk factors for tinnitus are needed.

http://www.amjmed.com/article/S0002-9343(10)00344-X/fulltext

Obesity's Effects on Sexuality

 Bajos N et al. BMJ 2010 Jun 15; 340:c2573

Goldbeck-Wood S. BMJ 2010 Jun 15; 340:c2826

Compared with normal-weight individuals, obese men reported more erectile dysfunction; obese women did not report more sexual dysfunction but were more likely to report unintended pregnancies.

Obesity's negative effects on overall health are clear, but its effects on sexual health are less well known. French investigators analyzed results of a national survey of sexual behaviors in 4635 men and 5535 women (age range, 18–69). In all, 9% of men and women were obese (body-mass index  30.0 kg/m²); 21% of women and 35% of men were overweight (BMI, 25.0–29.9).

Among younger women (age range, 18–29), those who were obese were threefold more likely to have met a partner on the Internet and were more likely to have obese partners than were normal-weight women. Whereas obese men experienced erectile dysfunction at twice the rate reported by normal-weight men, obese women were no more likely than normal-weight women to report sexual dysfunction (e.g., lack of arousal, painful intercourse). Obese women of all ages were less likely to have seen a clinician for contraception during the past year despite being sexually active (adjusted odds ratio, 0.37); younger obese women were less likely to have used oral contraception at last intercourse (AOR, 0.34), more likely to use withdrawal as a birth control method (AOR, 8.51), and more likely to report unintended pregnancies (AOR, 4.26).

http://www.ncbi.nlm.nih.gov/pubmed/20551118?dopt=Abstract

What's the relation to heart disease when the BMI is 25 kg or more?
These authors conclude that a BMI equal to or less than 25kg/m2 is common in patients with coronary heart disease. A U-shaped association, with highest risk among lean and obese patients, is persistent regardless of risk factor presence. Further data are required to support the need of aggressive weight reduction in patients with BMIs greater than 30kg/m2.

http://www.ajconline.org/article/S0002-9149(10)00941-0/fulltext

When obesity does no harm
This study concluded that among patients with established atrial fibrillation, overweight and obesity do not adversely affect overall survival. Obesity does not appear to impact the relative benefit of a rate or rhythm control strategy.

 In conclusion, in patients with established AF, overweight and obesity do not adversely affect overall survival. Obesity does not appear to affect the relative benefit of a rate- or rhythm-control strategy.

http://www.ajconline.org/article/S0002-9149(10)00785-X/fulltext

When the bad cholesterol is good, the good cholesterol hardly matters
Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60713-1/abstract

Vitamin D Deficiency Associated with Dementia and Parkinson Disease

Two studies seem to point to vitamin D deficiency as having a role in both cognitive decline and Parkinson disease, but commentators aren't certain about the clinical implications.

One study, published in the Archives of Internal Medicine, followed some 850 older adults for about 6 years. Low serum levels of vitamin D at the outset of the study were associated with substantial cognitive decline (as measured by the Mini-Mental State Examination) by study's end. Editorialists caution that "low vitamin D levels may simply be a marker for lower health status than a cause of it." They write that "a rigorous evidence base ... does not currently exist" to favor using vitamin D supplementation to improve health outcomes.

The other study, published in the Archives of Neurology, found an association between low levels of vitamin D and the development of Parkinson disease by follow-up some 30 years later. An editorialist finds the results promising but preliminary

Conclusions  The results are consistent with the suggestion that high vitamin D status provides protection against Parkinson disease. It cannot, however, be excluded that the finding is due to residual confounding and further studies are thus needed.

http://archneur.ama-assn.org/cgi/content/short/67/7/808

Aspirin for Primary Prevention in Patients with Diabetes

Recommendations from three professional organizations

The American Heart Association, the American College of Cardiology, and the American Diabetes Association have collaborated to produce a position statement on aspirin for primary prevention in patients with diabetes. The statement includes a meta-analysis of nine randomized trials, in which aspirin lowered risk for coronary events by 9% and for stroke by 15%; neither difference reached statistical significance. The authors estimate thatexcess risk for gastrointestinal bleeding conferred by aspirin could be as high as 1 to 5 episodes per 1000 diabetic patients annually. Based on their balancing of benefits and harms, the authors make the following recommendations for primary prevention in adults with diabetes:

Low-dose aspirin (75–162 mg daily) "is reasonable" for patients with 10-yearcardiovascular disease (CVD) risk >10% and no risk factors for bleeding. This group would include most diabetic men older than 50 and women older than 60 who have at least one additional major risk factor (i.e., smoking, hypertension, dyslipidemia, family history of premature CVD, or albuminuria).

Aspirin "should not be recommended" for diabetic men younger than 50 and women younger than 60 with no other risk factors (10-year CVD risk, <5%).

Aspirin "might be considered" for those at intermediate risk (10-year CVD risk, 5%–10%); this group would include younger patients with, and older patients without, other risk factors.

Several websites with calculators to estimate 10-year cardiovascular risk are listed, including the UKPDS Risk Engine and the ARIC CHD Risk Calculato

http://circ.ahajournals.org/cgi/content/full/121/24/2694?linkType=FULL&resid=121/24/2694&journalCode=circulationaha

Vitamin D and Cognitive Function in Older Patients

Low levels are associated with cognitive decline.

Vitamin D deficiency is associated with several chronic illnesses, but studies of its association with cognitive function have been short and have yielded equivocal results. Data from the well-known InCHIANTI study of older Italian people (J Am Geriatr Soc 2000; 48:1618) were used to determine the relation between cognitive decline among 858 participants (mean age at baseline, 74) and baseline levels of 25-hydroxyvitamin D (25[OH]D). 25(OH)D levels were classified as severely deficient (<10 ng/mL [<25 nmol/L]), deficient (10–20 ng/mL [25–50 nmol/L]), insufficient (20–30 ng/mL [50–75 nmol/L]), and sufficient ( 30 ng/mL [ 75 nmol/L]). Patients were assessed at baseline and every 3 years with several cognitive tests, including the Mini-Mental State Examination (MMSE).

At 6 years, analyses that were adjusted for clinical factors relevant to cognitive functions and for impaired mobility showed that participants with severe deficiency were 60% more likely to experience significant declines of  3 points on the MMSE than were participants with sufficient levels of 25(OH)D. Similar relative risks were noted for most secondary measures of cognition

A careful look at vitamin D and ovarian cancer
According to this systematic review, there is no consistent or strong evidence to support the claim made in numerous review articles that vitamin D exposures reduce the risk for ovarian cancer occurrence or mortality.

http://www.ajog.org/article/S0002-9378(10)00092-X/fulltext

Medical groups call for osteoporosis screening in high-risk men
Despite the lack of research on men's risk for osteoporosis, the National Osteoporosis Foundation and the American College of Physicians have decided to recommend bone-density testing for men at high risk, including those over 65 or 70. The National Institute of Arthritis and Musculoskeletal and Skin Diseases estimates that 6% of all men will experience a hip fracture after age 50 as a result of osteoporosis

 http://www.usatoday.com/news/health/painter/2010-07-26-yourhealth26_ST_N.htm

The cardiac dangers of a high-fructose diet
Indications of cardiac oxidative stress in mice were observed to occur within six weeks independently of systemic insulin dysregulation, showing that the myocardium responds to a high-fructose diet in the absence of marked systemic pathology. The investigation also suggests that the young are particularly susceptible to the cardiac effects of high-fructose intake.

Conclusion

These findings indicate that increased myocardial superoxide production may represent an early and primary cardiac pathologic response to the metabolic challenge of excess dietary fructose in juveniles and adults that can be detected in the absence of cardiac hypertrophy and hypertension.

 http://www.nutritionjrnl.com/article/S0899-9007(09)00342-6/fulltext  

 Calcium channel blockers, hypertension and heart failure. What's the connection?
These results suggest that patients with hypertension treated with calcium channel blockers have increased incident heart failure.

http://www.ajconline.org/article/S0002-9149(10)00690-9/fulltext

Walnuts, oxidant status and mice
This study investigated whether the oxidation of polyunsaturated fatty acids from walnuts could be compensated for by the antioxidant compounds they contain. Results showed that, although plasma antioxidant capacity decreased in mice on walnut and walnut-skin diets, in comparison with the control group, the plasma oxidizing capability seemed to be preserved.

http://www.nutritionjrnl.com/article/S0899-9007(09)00371-2/fulltext

What does cardiorespiratory fitness predict?
The results of this study suggest that cardiorespiratory fitness is a coronary heart disease risk factor, largely independent of physical activity, which warrants clinical screening.

http://www.ajconline.org/article/S0002-9149(10)00693-4/fulltext 

 Guidelines call for MRI, not CT for stroke diagnosis
New American Academy of Neurology guidelines support study data showing diffusion magnetic resonance imaging is better than computed tomography for diagnosing strokes caused by lack of blood flow to the brain. Many physicians prefer using a CT scan because it usually is more readily available and takes less time to administer.

http://www.suntimes.com/lifestyles/2492330,CST-NWS-health13.article

Bystander CPR Studies Seem to Confirm Value of Compression-Only Approach

Having bystanders initiate compression-only CPR after cardiac arrest is at least as effective as using compression plus rescue breathing, according to two studies in the New England Journal of Medicine.

Both studies used emergency telephone dispatchers to instruct bystanders to use either compression-only or standard CPR until emergency medical services personnel arrived. The dispatchers' recommended approach was governed by randomization. Patients with arrest due to trauma, asphyxiation, or drowning were excluded from both studies.

In the first study, undertaken in the U.S. and the U.K., over 1900 patients had similar rates of survival to hospital discharge — 12.5% with compression-only, and 11.0% with traditional CPR. Similarly, the second study, comprising nearly 1300 Swedish patients, found no advantage in 30-day survival rates — 8.7% with compression-only, and 7.0% with standard CPR.

Writing in Journal Watch Emergency Medicine, Dr. J. Stephen Bohan calls the findings "important, because doing away with [rescue] breathing might increase the prevalence of bystander CPR.

http://www.nejm.org/doi/full/10.1056/NEJMoa0908993

Probiotics to Reduce Nonsteroidal Anti-Inflammatory Enteropathy?

In a small crossover trial, a probiotic mixture reduced fecal calprotectin concentrations in healthy volunteers who were receiving indomethacin.

Probiotics to Reduce Nonsteroidal Anti-Inflammatory Enteropathy?

In a small crossover trial, a probiotic mixture reduced fecal calprotectin concentrations in healthy volunteers who were receiving indomethacin.

Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for upper gastrointestinal bleeding. Reducing gastric acid by using proton-pump inhibitors can mitigate this risk. NSAIDs can also damage the lower gastrointestinal tract, by an acid-independent mechanism, leading to increased intestinal permeability and blood loss. Intestinal bacteria are believed to play a role in such enteropathy.

Investigators in Italy recently studied the effect of a probiotic preparation on enteropathy associated with the NSAID indomethacin. Twenty healthy volunteers were randomized to receive either a probiotic mixture of eight bacterial strains or placebo daily for 21 days. All participants received 50 mg per day of indomethacin on days 16 to 19. Stool was collected at the beginning of the study and on days 15 to 21 for measurement of fecal calprotectin levels (a marker of intestinal permeability). Participants were crossed over to the other trial arm after an interval of  30 days.

When taking the placebo, participants had increased levels of fecal calprotectin on days 17 to 21, compared with baseline. When taking the probiotic, they had increased levels only on day 17. The authors conclude that this probiotic mixture reduces indomethacin-associated intestinal inflammation.

Comment: These findings are intriguing but must be interpreted cautiously. The trial was very small, and the range of fecal calprotectin levels was highly variable at each time point. The authors studied only an indirect marker of enteropathy that might not indicate changes in intestinal inflammation. Additional research is needed to confirm the potential role of probiotics in reducing NSAID enteropathy and to identify the optimal mixture of bacteria.

Published in Journal Watch Gastroenterology July 23, 2010

: Montalto M et al. Aliment Pharmacol Ther 2010 Jul 32:209

If Your Stomach Is Bigger, Is Your Brain Smaller?

Visceral fat is associated with smaller brain volume.

 Debette S et al. Ann Neurol 2010 May 20;

Blood Pressure Control in Patients with Diabetes and Coronary Artery Disease

No benefit for lowering BP to <130/80 mm Hg

Several organizations recommend a blood pressure (BP) goal of <130/80 mm Hg for patients with diabetes. To determine whether this goal is appropriate for patients with diabetes and known coronary artery disease (CAD), researchers conducted a secondary analysis of data from the INVEST study, a randomized trial in which hypertensive patients with CAD received β-blocker–based or calcium-channel blocker–based regimens (JW Gen Med Dec 23 2003). Researchers reported previously that overly aggressive BP lowering in these patients was associated with excess risk for adverse cardiovascular events (JW Gen Med Aug 10 2006); now, they focus on subset of 6400 INVEST patients with diabetes.

Patients were divided into three groups according to their average systolic BP during the trial: tight control (<130 mm Hg), usual control (130–139 mm Hg), or uncontrolled (>139 mm Hg). During median follow-up of 3 years, the primary outcome (all-cause mortality or nonfatal myocardial infarction or stroke) occurred in 12.7% of the tight-control group, in 12.6% of the usual-control group, and in 19.8% of the uncontrolled group. In adjusted analyses that included secondary outcomes, researchers found no difference between tight and usual control. After an additional 5-year follow-up, all-cause mortality was higher in the tight-control group than in the usual-control group (22.8% vs. 21.8%; P=0.04).

Comment: Because this was a post hoc analysis of observational data from patients who weren't randomized to different BP targets, confounding factors could have influenced the findings. However, in the recently published ACCORD BP trial, high-risk patients with diabetes were randomized to one of two systolic BP targets (120 mm Hg or 140 mm Hg), and researchers found no difference in adverse cardiovascular events between the groups (JW Cardiol Mar 14 2010). Taken together, INVEST and ACCORD suggest that a systolic BP goal in the 130s is reasonable for hypertensive diabetic patients with CAD or multiplecardiovascular risk factors.

 Cooper-DeHoff RM et al. JAMA 2010 Jul 7; 304:61

http://www.ncbi.nlm.nih.gov/pubmed/20606150?dopt=Abstract

Short Telomeres Are Associated with Excess Cancer Incidence and Mortality

A prospective study suggests that telomere length and cancer incidence are related.

Willeit P et al. JAMA 2010 Jul 7; 304:69

Stroke Risk Grows with Waistlines in U.S. Women

According to U.S. survey data, rising obesity is associated with rising midlife stroke rates in women, but not in men.

 Towfighi A et al. Stroke 2010 May 27;

Statins and Primary Prevention for Patients at High Risk for Heart Disease

The benefit, if any, is very small.

Statins — which clearly confer an all-cause mortality benefit in patients with knowncardiovascular disease (CVD) — are prescribed extensively for primary prevention in patients at high CVD risk but without CVD. Two groups of investigators examined evidence for this practice.

European investigators combined results for only high-risk patients without known CVD from 11 randomized controlled trials, including some previously unpublished data from the original investigators, to assess all-cause mortality in 65,000 patients (age range, 51–75). During average follow-up of nearly 4 years, the mean LDL cholesterol level was 134 mg/dL in placebo recipients and 94 mg/dL in statin recipients. Nearly 2800 deaths occurred, with about 100 fewer deaths in the treated group, for a risk ratio of 0.91 (roughly 7 fewer deaths per 10,000 person-years of treatment); the difference was not significant (95% confidence interval, 0.83–1.01).

In a related article, several authors critiqued the JUPITER study, which showed a significant benefit from primary prevention with rosuvastatin in patients without known CVD but with high-sensitivity C-reactive protein (hsCRP) levels (JW Gen Med Dec 29 2008). Among the authors' criticisms are (1) several secondary outcomes were used as justification for stopping the trial early when only a few major clinical events had occurred; (2) the apparent convergence of the all-cause mortality curves when the trial was stopped suggests that longer follow-up would have eliminated between-group differences; (3) an unexpectedly lowmortality rate from CVD, as well as an unexpectedly low case-fatality rate from myocardial infarction at the time of early termination, suggests the potential for undetected bias; (4) manufacturer involvement in the conduct of the study was substantial; and (5) 9 of the 14 JUPITER investigators had potential conflicts of interest.

Comment: Unsurprisingly, these studies have created a firestorm of debate. Authors of one editorial sum up the JUPITER controversy by noting that nothing can be said about the value of hsCRP for primary prevention with statins when patients with low hsCRP levels were not included in the trial, that stopping a trial early tends to exaggerate the apparent benefits and minimize the potential harms of a study, and that these results should not distract us from focusing on known risk factors and benefits of lifestyle modification. Another editorialist sums up the issue by saying that "in the short term, for true primary prevention, the benefit, if any, is very small."

 Moderate Caffeine Consumption Does Not Cause Miscarriage,Preterm Birth

Moderate caffeine consumption (<200 mg/day) — about a cup of brewed coffee daily — does not appear to increase a woman's risk for miscarriage or preterm birth, according to a statement from the American College of Obstetricians and Gynecologists.

A review of recent studies on caffeine consumption and pregnancy outcomes revealed the following:

Miscarriage: One prospective study showed no increase in miscarriage risk at all levels of caffeine consumption, while another found a doubling of risk for women who consumed more than 200 mg daily.

Preterm birth: Two studies found no association between caffeine intake and preterm birth (average intake in one study, 182 mg/day).

Intrauterine growth restriction: Findings were equivocal; the committee concluded that the relationship between caffeine consumption and IUGR is "undetermined."

ACOG committee opinion in Obstetrics & Gynecology 

Antibiotic-Induced Hyperkalemia and Renin-Angiotensin–System Inhibitors

Among older patients who were receiving renin-angiotensin–system inhibitors, trimethoprim-sulfamethoxazole (but not other antibiotics) increased the risk for hyperkalemia.

Recent years have seen greatly increased use of renin-angiotensin system inhibitors, including angiotensin-converting–enzyme inhibitors and angiotensin-receptor blockers. With this increase, we should expect a rise in novel drug interactions.

Knowing that hyperkalemia has been associated both with renin-angiotensin–system inhibitors and with trimethoprim, investigators in Toronto performed a population-based, nested case-control study among older patients (aged  66) who were receiving continuous treatment with one of these blockers and had also been prescribed trimethoprim-sulfamethoxazole (TMP-SMX), ciprofloxacin, norfloxacin, nitrofurantoin, or amoxicillin. Cases (371 patients who were hospitalized between 1994 and 2008 for treatment of hyperkalemia  14 days after receiving an antibiotic of interest) were each matched with one to four controls (similar patients without such hospitalization before the index date).

The risk for hyperkalemia-associated hospitalization within 14 days of antibiotic prescription was nearly sevenfold higher with TMP-SMX than with amoxicillin (adjustedodds ratio, 6.7; 95% confidence interval, 4.5–10.0). Findings were similar when the index hospitalization occurred within 7 days of antibiotic prescription. No association was seen between use of any of the other study antibiotics and development of hyperkalemia.

http://www.ncbi.nlm.nih.gov/pubmed/20585070?dopt=Abstract

Microvascular Outcomes in the ACCORD Trial

Intensive glycemic control did not lower the incidence of microvascular adverse outcomes.

In the ACCORD trial, 10,000 patients with type 2 diabetes (mean age, 62; average duration of diabetes, 10 years) were randomized to receive intensive or standard glycemic control; choice of antidiabetic agents was individualized. The main purpose of ACCORD was to determine whether intensive treatment (target glycosylated hemoglobin [HbA_1c] level,  6%) improved cardiovascular outcomes. The trial was halted after an average follow-up of 3.5 years, when overall and cardiovascular mortality were significantly higher with intensive than with standard treatment (JW Gen Med Jun 6 2008). Now, the researchers present microvascular outcomes.

The principal composite microvascular outcome was end-stage renal disease, rise of serum creatinine to >3.3 mg/dL, or need for photocoagulation or vitrectomy to treat retinopathy. This outcome occurred in similar proportions of patients in the intensive and standard treatment groups, both during the study itself (9%) and after 1.5 additional years of follow-up (11%). Although intensive treatment appeared to slow the progression of neuropathy, the incidence of a composite endpoint that included neuropathy (along with nephropathy and retinopathy) remained similar between groups. Some secondary endpoints (e.g., incident albuminuria) occurred less often with intensive than with standard therapy.

High Thyroxine Levels and Risk for Venous Thrombosis

Data from a case-control study suggest there might be a link.

Hyperthyroidism is associated with a hypercoagulable state. Conversely, hypothyroidism is associated with reduced levels of von Willebrand factor and increased risk for bleeding. To investigate the relation between hyperthyroidism and risk for venous thrombosis, researchers in the Netherlands measured thyroid-hormone and thyroid-antibody levels in 190 patients with a first deep venous thrombosis (DVT) and 379 sex-matched controls.

The mean level of free thyroxine was significantly higher among DVT patients than among controls (16.2 pmol/L vs. 15.4 pmol/L; P<0.01), as was the mean T₃ level (1.90 nmol/L vs. 1.79 nmol/L; P<0.01). The higher the thyroxine level, the greater the risk for DVT, such that a level above the reference threshold (>24 pmol/L) was associated with an age- and sex-adjusted odds ratio for DVT of 13.0 (95% confidence interval, 1.1–154.1).

Thyrotropin levels tended to be higher in DVT patients than in controls, but they were not significantly associated with risk for DVT, particularly after adjustment for free thyroxine levels. Levels of thyroid peroxidase antibodies did not differ significantly between DVT patients and controls. Three DVT patients and no controls had overt hyperthyroidism (P=0.02).

Comment: The observational finding that increased thyroid activity is a risk factor for DVT is not intuitively obvious. Patients with hyperthyroidism usually have a hyperdynamic circulation rather than the sluggish blood flow that characterizes venous thrombosis. The investigators suggest that thyroid hormone–induced increases in factor VIII are responsible for the thrombophilia, but they did not use clotting-factor assays to confirm this. It is also possible that thyroid hormone is a surrogate for some other thrombogenic factor. Only large epidemiologic studies can confirm whether a high level of thyroid hormones is a risk factor for DVT. Until then, clinicians confronted with unexplained venous thrombosis might simply consider hyperthyroidism as a possibility.

http://www.ncbi.nlm.nih.gov/pubmed/20308594?dopt=Abstract

                                       Understanding the "Other" Human Genome: The Microbiome

Nine of 10 cells in or on our bodies belong to our live-in microbial symbionts.

Each of us is colonized, inside and out, by microorganisms — more than 3 pounds of microorganisms in our gut, and many more on our skin. In fact, we harbor 10 microbial cells for every 1 of our own cells. If our microbial partners were merely fellow travelers with no effects on our health, their invisible presence would be of little interest. However, we have known for a long time that gut bacteria do affect our health.

Gut microbes produce molecules that travel through the enterohepatic circulation or breach damaged gut barriers; these microbial molecules include anti-inflammatory factors, analgesic compounds, antioxidants, and vitamins. In addition, toxins produced by gut bacteria can cause serious disease. In recent years, surprising evidence has emerged that even links gut bacteria to obesity (JW Gen Med Jan 2 2007), diabetes, and several cancers.

A huge international effort, the Human Microbiome Consortium, is under way to sequence the genes of all our microbial partners. This will be a tall order, as the microbes that colonize us have, collectively, 100 times more genes than we do, and those genes appear to have more variants than our genes do. So far, the genomes of 178 microbes (out of the roughly 1000 that colonize us) have been sequenced. Whether this effort ultimately helps to protect human health remains to be seen.