Archief Roodbont

Abstract and Introduction
Abstract

Objective Studies in rodents indicate a role of vitamin D in male reproduction, but the relationship between vitamin D and androgen levels in men is largely unexplored. We aimed to investigate the association of 25-hydroxyvitamin D [25(OH)D] levels with testosterone, free androgen index (FAI) and SHBG. Moreover, we examined whether androgen levels show a similar seasonal variation to 25(OH)D.
Design In this cross-sectional study, 25(OH)D, testosterone and SHBG levels were assessed by immunoassay in 2299 men who were routinely referred for coronary angiography (1997–2000).
Measurements Main outcome measures were associations of 25(OH)D levels with testosterone, SHBG and FAI. FAI was calculated as testosterone (nmol/l)/SHBG (nmol/l) × 100.
Results Men with sufficient 25(OH)D levels (≥30 μg/l) had significantly higher levels of testosterone and FAI and significantly lower levels of SHBG when compared to 25(OH)D insufficient (20–29·9 μg/l) and 25(OH)D-deficient (<20 μg/l) men (P < 0·05 for all). In linear regression analyses adjusted for possible confounders, we found significant associations of 25(OH)D levels with testosterone, FAI and SHBG levels (P < 0·05 for all). 25(OH)D, testosterone and FAI levels followed a similar seasonal pattern with a nadir in March (12·2 μg/l, 15·9 nmol/l and 40·8, respectively) and peak levels in August (23·4 μg/l, 18·7 nmol/l and 49·7, respectively) (P < 0·05 for all).
Conclusion Androgen levels and 25(OH)D levels are associated in men and reveal a concordant seasonal variation. Randomized controlled trials are warranted to evaluate the effect of vitamin D supplementation on androgen levels.

Dual, triple anticoagulation therapy for AF may triple bleeding risk

16 September 2010

MedWire News: Adding clopidogrel, with or without aspirin, to warfarin in anticoagulation therapy for atrial fibrillation (AF) may increase patients’ bleeding risk at least three-fold, research indicates.

This risk is much higher than previously recognized, and further still, such combination therapy does not appear to notably reduce nonfatal and fatal ischemic stroke risk, say Morten Hansen (Copenhagen University Hospital, Denmark) and colleagues.

The researchers used national registries to assess the post-discharge medications and outcomes of 118,606 Danish patients admitted to hospital for AF.

Patients who collected at least one prescription for a medication after discharge were assumed to have taken the medication.

Hansen et al found that 86.1% of patients took warfarin, aspirin, or clopidogrel monotherapy after discharge.

Dual warfarin-aspirin therapy was more commonly taken after discharge than warfarin-clopidogrel, or clopidogrel-aspirin, at 15.5%, 1.2%, and 2.4%, respectively.

Only 1.1% (n=1261) of patients took warfarin-aspirin-clopidogrel triple therapy.

The findings, published in the Archives of Internal Medicine, showed that over a mean follow-up period of 3.3 years, 11.4% of patients experienced fatal or nonfatal bleeding.

The team found that the highest rates of bleeding occurred among patients taking triple therapy or dual warfarin-clopidogrel therapy, at 15.7% and 13.9%, respectively.

When compared with warfarin monotherapy in Cox proportional hazards modeling, triple therapy and any dual therapy were associated with a significantly increased risk for fatal and nonfatal bleeding, with aspirin-clopidogrel, warfarin-aspirin, warfarin-clopidogrel, and triple therapy each associated with 1.66-, 1.83-, 3.08-, and 3.70-fold increases in risk for fatal and nonfatal bleeding, respectively.

Of note, the risk for ischemic stroke remained higher among patients on aspirin-clopidogrel, warfarin-aspirin, or triple therapy than among those on warfarin monotherapy, with 1.56-, 1.27-, and 1.45-fold risk increases, respectively.

And although warfarin-clopidogrel dual therapy reduced ischemic stroke risk, by 30%, the reduction was nonsignificant.

The researchers conclude: “These results stress that appropriate selection of patients for these therapies is important and that physicians should consider the expected benefits and risks carefully before prescribing combination therapy.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Arch Intern Med 2010; 170: 1433–1441

Prevention better than cure for CHD

21 September 2010

MedWire News: Researchers report that recent declines in death from coronary heart disease (CHD) in the US are largely attributable to reductions in modifiable risk factors such as systolic blood pressure (SBP).

Although secondary prevention accounted for some of the observed reduction in mortality rates, the majority (79%) of improvement was due to the primary prevention of CHD by reducing risk factors among healthy individuals, explain Fiona Young from Newcastle University in the UK, and colleagues.

The researchers used the IMPACT model (Estimating the Effect of Population Risk Factor Trends on Coronary Heart Disease Mortality) to determine risk factor decline and subsequent CHD mortality rates among US patients with and without CHD, from 1980 to 2000.

The contribution of three risk factors – smoking, systolic blood pressure (SBP), and cholesterol – to a decline in CHD mortality over the 20-year period was estimated using a regression model and data from the National Center for Health Statistics in 1980 and in 2000.

Writing in the American Journal of Preventive Medicine, Young and colleagues report that 341,745 fewer deaths occurred in 2000 than in 1980 (43% reduction). Of these, 316,100 were attributed to reductions in the three assessed CHD risk factors.

The team found that risk factor modification by existing CHD patients and asymptomatic individuals contributed to 21% and 79% of the observed improvement in mortality rates, respectively.

The researchers also found that cholesterol reduction produced the greatest fall in mortality of the assessed risk factors, with 22,210 and 107,300 fewer deaths in 2000 compared with 1980, among CHD patients and asymptomatic individuals, respectively.

SBP reduction produced 34,330 and 97,555 fewer deaths among CHD patients and asymptomatic individuals, respectively, and smoking reduction accounted for the smallest decline in CHD mortality, with a respective 8390 and 46,315 fewer deaths.

“Primary prevention tends to be underexploited and undervalued in comparison with other methods of reducing CHD mortality,” comment Young et al.

They conclude: “The large recent reductions in CHD mortality attributable to primary prevention in the US suggest that population-based intervention, state, and federal policies, and societal changes might substantially reduce future coronary deaths.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Am J Prev Med 2010; 39: 228–234

September 24, 2010 — Lower serum folate levels appear to be associated with an increased risk for depressive symptoms, a large population-based, cross-sectional study suggests.

Data on US adults from the National Health and Nutrition Examination Survey (NHANES) show elevated depressive symptoms were inversely associated with folate status, particularly among women.

"We found that the odds of having elevated depressive symptoms among individuals with the highest serum folate levels were about half that of those with the lowest levels," lead investigator May A. Beydoun, PhD, MPH, National Institute on Aging, told Medscape Medical News.

The study was published online September 14 in Psychosomatic Medicine.

First Nationally Representative Study

Previous research indicates that high levels of total homocysteine (tHcy) and low levels of folate and vitamin B12 are associated with depression or elevated depressive symptoms in adults.

However, investigators note that earlier studies examining the impact of low folate, low vitamin B12, and elevated tHcy status simultaneously on depressive symptoms did not examine interaction among those 3 risk factors and have had inconsistent findings as to the individual associations.

"To our knowledge this is the first nationally representative study conducted among U.S. adults after mandatory fortification of food with folic acid that examines associations of serum folate, vitamin B12, and tHcy levels with depressive symptoms," they write.

For the study the researchers used cross-sectional data from NHANES from 2005 to 2006 by assessing interactions (2 way and 3 way) among the 3 exposures and testing effect modification of the associations by sex.

The study sample included 2524 adults aged 20 to 85 years with complete data on demographics, diet, plasma folate, vitamin B12, and tHcy status, as well as information on physical activity, smoking status, blood pressure, and depressive symptoms.

Depressive symptoms were measured using the Patient Health Questionnaire (PHQ), and elevated symptoms were defined as a PHQ total score of 10 or greater.

Study Underpowered to Detect Effect in Men

With an odds ratio of 0.52 (95% confidence interval [CI], 0.35 – 0.76), adjusted analyses revealed that among the total population the odds of having elevated depressive symptoms was close to half that in the lowest tertile.

Further, with an odds ratio of 0.37 (95% CI, 0.17 – 0.86), the likelihood of women in the highest tertile of serum folate (mean ± SE, 21.1 ±0.29 ng/mL) to experience elevated depressive symptoms was about a third that of their counterparts in the lowest tertile (7.02 ± 0.08 ng/mL).

The study showed no relationship between B12 and tHcy levels and elevated depressive symptom risk — a finding that is consistent with previous research the researchers note.

In addition, researchers report that B12 and tHcy did not interact with folate status to affect its inverse association with depressive symptoms among women.

However, elevated homocysteine level was positively associated with elevated depressive symptoms in adults 50 years and older.

Although a significant association between folate levels and risk for elevated depressive symptoms was only observed in women, the investigators believe this is because the study was underpowered to detect the effect in men.

Boosting Folate Levels

The investigators point out that although the study has several strengths, it also has limitations, including its cross-sectional design, which prevents examination of the relationship between depression and serum folate levels over time.

Therefore, they note, it is possible that reverse causality is at play such that depressed individuals may be more likely to have a poor diet and therefore lower folate intake than nondepressed individuals.

Future interventions to improve mental health outcomes among US adult should focus on increasing levels of serum folate say investigators.

For instance, said Dr. Beydoun, clinicians should consider screening patients with depressive symptoms for serum folate and, if indicated, consider supplementation in addition to standard antidepressant therapy.

In addition, dietary and lifestyle advice to enhance serum folate should also be considered. Such counseling, she said, should include education about folate-rich foods, the beneficial effect of physical activity on folate levels, and the negative impact of cigarette smoking.

Diet Important in Mental Health

Commenting on the study, Felice Jacka, PhD, a researcher from the University of Melbourne in Australia, who has conducted a number of studies examining the impact of diet on mental health status, said given the fact that previous studies have reported this relationship the results are not surprising.

"However," she said, "the NHANES data are very good quality and, therefore, a very good vehicle to examine the relationships between nutritional status and mental health."

"This is the first large-scale population-based study in the US to show that folate status is associated with the presence of depressive symptoms since the fortification of foods with folate became mandatory," she added.

Dr. Jacka said this study also lends further support to the premise that diet is an important factor for mental health in the general population.

"It also suggests that blood tests to examine folate and homocysteine levels (and levels of other nutrients) in individuals with depressive symptoms may be of utility in clinical settings. If nutrient deficiencies and/or excess homocysteine are identified, dietary and/or supplementation strategies could then be considered," she said.

The study authors have disclosed no relevant financial relationships.

Psychosom Med. Published online September 14, 2010.

September 23, 2010 — In a British national survey of older adults, clinical vitamin D deficiency, defined as a serum 25-hydroxyvitamin D (25[OH]D) level less than 10 ng/mL, was significantly associated with depressive symptoms, independent of age, sex, social class, physical health status, and season.

Milder states of vitamin D deficiency were not strongly associated with depression in older adults, Robert Stewart, MD, of King's College London, and Vasant Hirani, MSc, of University College London, United Kingdom, report in the September issue of Psychosomatic Medicine.

"Although vitamin D deficiency has been investigated in relationship to mental disorders in younger adults, relatively little research has investigated this association in older people, despite the higher potential impact," the study authors write.

They analyzed data on 2070 adults 65 years and older who participated in the 2005 Health Survey for England. As part of the survey, information on health and health behaviors and sociodemographic data were collected, 25(OH)D levels were measured, and depressive symptoms scored using the Geriatric Depression Scale.

The directly measured vitamin D levels, the use of a widely used scale for depression in older adults, and the large nationally representative sample are key advantages of the study, the study authors say.

Independent Risk Factor

Overall, about one-quarter of the cohort (25.2%) had depressive symptoms, they report. The prevalence of depressive symptoms was 22.6% in the 85.4% of adults with 25(OH)D levels less than 30 ng/mL and 25.8% in the 51.4% of adults with 25(OH)D levels less than 20 ng/mL.

The prevalence of depression was highest (35.0%) in the 9.8% of the cohort with 25(OH)D levels less than 10 ng/mL (clinical deficiency).

The prevalence ratio for depressive symptoms in those with clinical vitamin D deficiency, relative to the remainder of the sample, was 1.45, the team notes, and the population-attributable fraction calculated from this was 4.2%.

In logistic regression analyses, associations between the 3 deficiency states and depression were significant before adjustment for covariates. After adjustment for age, sex, social class, season, smoking status, body mass index, long-standing limiting illness, and subjective general health status, only the association with clinical vitamin D deficiency remained significant and independent (odds ratio, 1.46; 95% confidence interval, 1.02 – 2.08; P = .04).

Further adjustment for alcohol intake and stratification by season of examination did not markedly or consistently alter the results, the researchers note.

Clinical Trial Warranted

Commenting on the study for Medscape Medical News, geriatrician and epidemiologist Luigi Ferrucci, MD, PhD, of the Clinical Research Branch of the National Institute on Aging in Baltimore, Maryland, who was not involved in the study, said there has been "a long series of papers" showing vitamin D deficiency is not only associated with bone problems but with a series of other problems, including low muscle strength, cognitive and vision problems, and depression.

"The studies on depression have been cross-sectional and the data were not very convincing for a number of reasons. The most important one, probably, is that if you have low vitamin D you are likely to have all these pathological problems associated with low vitamin D and these, by themselves, can cause you to be depressed."

Echoing this, Dr. Stewart and Mr. Hirani point out in their paper that "it is possible that depressive states were a cause, rather than a consequence, of vitamin D deficiency." However, if this were the case, they say the association with depression would be expected to be to a similar extent with any relative 25(OH)D deficiency rather than restricted to the 10% lowest levels, as was the case in the current study.

"Ultimately, prospective research is required to clarify the direction of cause and effect," the study authors note. Seconding that view, Dr, Ferrucci said, "An observational study is far from truly establishing causality, but there may be enough evidence at this point to start a clinical trial."

He believes we are reaching a "critical threshold of evidence where it may be worthwhile in investing in a clinical trial to study the effect of vitamin D supplementation on depression risk."

In such a study, Dr. Ferrucci explained, "we'd take people with no depression at baseline, but maybe at risk for depression, treat them with vitamin D or placebo, and what we'd expect to see is that those treated with vitamin D will be less likely to develop a depressive episode in the future; if we could demonstrate that, then the causal pathway is more likely, but we are not at that stage yet."

If vitamin D deficiency is demonstrated to be a cause of depression, correcting the problem "could be an effective public health measure to reduce depression prevalence in later life," Dr. Stewart and Mr. Hirani conclude in their report.

The study authors and Dr. Ferrucci have disclosed no relevant financial relationships.

Psychosom Med. 2010;72:608-612.

Cardiovascular and Cancer Mortality in Very Elderly Post-Myocardial Infarction Patients Receiving Statin Treatment

Melvin Cheitlin

Authors and Disclosures

Posted: 09/16/2010; Faculty of 1000 Medicine © Medicine Reports Ltd.
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Gränsbo K, Melander O, Wallentin L, Lindbäck J, Stenestrand U, Carlsson J, Nilsson J
J Am Coll Cardiol 2010 Mar 30 55(13):1362-9
Commentary from Melvin Cheitlin

Changes Clinical Practice: Statins, at the maximum safe dosage for the particular statin being prescribed, should be used to reduce the cardiovascular mortality of acute myocardial infarction patients aged 80 or over (statins can be prescribed without increasing the incidence of cancer).

There are excellent data for the effectiveness of statins in decreasing mortality in patients with an acute myocardial infarction. However, in many of the studies there were few or no very elderly patients. This study gives evidence of the effectiveness of statin therapy in decreasing mortality in very elderly patients after an acute myocardial infarction. Many physicians are wary of starting statins in very elderly post-infarction patients because of possible side effects, the relatively sparse evidence of effectiveness in this age group, the fear that statins increase the incidence of cancer and (with the expectation that the patient's life-span being very limited) that any long-term benefit from the statins would not be expected. This study should put these fears to rest.

This study addresses a problem with evidence-based therapy in that studies often exclude very old patients. Elderly patients are excluded in these studies because they have a greater number of comorbidities that could obscure the benefit of the studied therapy. In this paper, the evidence shows that statin therapy increases survival after an acute myocardial infarction in patients aged 80 years and older. The follow-up time of a median 296 days, maximum 5 years, showed the total mortality and the cardiovascular mortality to be decreased by 45% and similar reductions occurred in cardiovascular mortality in those patients taking a statin. The mortality outcomes were similar where patients who died within 14 days of the acute event were excluded, as well as all patients who died within the first year after the acute event. This is very good evidence of the effectiveness of statins even in very old patients who have an acute myocardial infarction. For additional background reading, please see refs.[

September 9, 2010 — In an about face of findings, a new study reports that oral bisphosphonates — widely prescribed for osteoporosis — are associated with an increased risk for esophageal cancer. The study comes just weeks after another study, using the same database, found no such link.

The new case–control study found that the risk was statistically significant among patients who had 10 or more prescriptions for the drugs — compared with patients who had 1 to 9 prescriptions.

The relative risk also increases with duration of use; it doubles over about a 5-year period, according to the authors of the new study, led by Jane Green, PhD, a clinical epidemiologist from the Cancer Epidemiology Unit at the University of Oxford in the United Kingdom.

However, an expert in gastroesophageal cancer contacted by Medscape Medical News suggested that clinicians should not stop prescribing oral bisphosphonates.

Clinicians need to weigh the benefits of oral bisphosphonates such as the reduction in hip fracture against the risks such as the increase in esophageal cancer, said Gerard Blobe, MD, associate professor of medicine at Duke University School of Medicine in Durham, North Carolina.

"The absolute risk increase found in the study is still pretty small — 1 in 1000 to 2 in 1000 with about 5 years of use of oral bisphosphonates," he observed about the new data.

"I would say that, generally, the benefits outweigh the risks," he said.

Dr. Blobe also explained that oral bisphosphonates could theoretically cause esophageal cancer because "irritation" of the esophagus might "set the stage for cancer in some patients."

The new study's findings on oral bisphosphonates conflict with a recent British study that found no link.

Notably, both studies used the UK General Practice Research Database.

"What would cause these differences [in findings]?" asks an editorial that accompanies the new study, both of which were published online September 2 in BMJ.

A "major difference" in the 2 studies is the average length of follow-up, notes the editorialist, Diane Wysowski, PhD, an epidemiologist at the US Food and Drug Administration (FDA) in Silver Spring, Maryland. The earlier negative study had 4.5 years of follow-up; the new positive study has 7.5 years.

The positive study also had "an adequate sample size," said Dr. Wysowski.

Dr. Green and her coauthors said that their positive study had "greater statistical power" than the negative study — with 5 matched controls per case, compared with equal numbers in the exposed and comparison groups in negative study.

Even if oral bisphosphonates cause cancer, "the incidence of esophageal cancer in this population of users would be expected to remain relatively low," writes Dr. Wysowski.

Despite this comment, another gastroenterologist from Duke said that esophageal cancer is of growing concern in the United States and other industrialized countries.

"The incidence of esophageal adenocarcinoma is rising more rapidly than any other malignancy in the past 5 years in Western countries. The reasons are unknown," said Ivy Altomare, MD, assistant professor of medicine and a colleague of Dr. Blobe.

Advice to Patients

The immediate question for clinicians is what to tell patients, says Dr. Wysowski. Her primary recommendation is to tell patients to take the pills correctly. Dr. Blobe explained the reason for the recommendation.

As soon as it was recognized that oral bisphosphonates were associated with esophageal problems, the package inserts for these drugs were changed, he said. The change included directions on how to best take the drugs, and dictated that patients with a history of esophageal problems not be prescribed these agents.

After the package insert was changed, "the incidence of esophageal-related problems with the drugs subsequently dropped," he said. This chain of events suggests that noncompliant patients might be the ones who develop problems, he said.

Dr. Wysowski reminds clinicians to reinforce directions for drug usage with each prescription. Namely, remind patients to take oral bisphosphonates in the morning with a full glass of plain water on an empty stomach — at least 30 to 60 minutes before the first food, beverage, or medication.

Also tell patients not to recline for at least 30 to 60 minutes after taking an oral bisphosphonate.

The new study results might be, in an odd way, useful to clinicians, suggested Dr. Blobe. "This result could incentivize patients to take the pill correctly," he said.

I have described a hyperlipidemic patient whose ability to utilize statins was previously compromised by statin-induced myalgias which did not recur following the correction of her vitamin D deficiency. Patients who are intolerant of statin therapy should be evaluated for vitamin D deficiency since vitamin D therapy has the potential to enable hyperlipidemic subjects to utilize these life saving drugs.
Sidebar

Summary and Comment
More Good News About Dabigatran

Dabigatran's advantages over warfarin are increased at centers with poor control of international normalized ratio in warfarin therapy.

The race is on to find an alternative to warfarin, which is currently the most effective agent for preventing stroke in patients with atrial fibrillation (AF) but has a narrow therapeutic range that is difficult and inconvenient to sustain. A new agent, dabigatran, has recently demonstrated noninferiority to warfarin in >18,000 patients with documented AF and at least one other risk factor for stroke who participated in RE-LY, a manufacturer-funded international trial (JW Cardiol Sep 1 2009). In a prespecified substudy, the RE-LY investigators divided the trial centers into quartiles by the average time participants on warfarin had international normalized ratios (INRs) within therapeutic range, and compared rates of the primary and secondary endpoints in the warfarin and dabigatran groups in each quartile.

Of 5791 participants assigned to warfarin, those treated at centers with higher rates of therapeutic INR time had lower risks for the composite endpoint of stroke and systemic embolism, major bleeding, and mortality than those treated at centers with lower rates of therapeutic INR time. At centers with lower rates of therapeutic INR time, dabigatran was associated with significant reductions in the composite endpoint of cardiovascular events and total mortality, as compared with warfarin.

Comment: In this study, poor control of INR in patients assigned to warfarin amplified the relative benefits of dabigatran. One would expect that patients who are enrolled in clinical trials would achieve better INR rates than patients who are not. Therefore, these findings suggest that in "real-life" clinical situations, the advantages of dabigatran over warfarin could be even greater than they were in the RE-LY trial.

— Mark S. Link, MD

Published in Journal Watch Cardiology August 30, 2010

Abstract and Introduction
Abstract

The renin-angiotensin-aldosterone system (RAAS) plays a major role in blood pressure regulation and is thus an important therapeutic target in the management of hypertension. Angiotensin receptor blockers (ARBs), which interrupt RAAS overactivity by blocking a specific receptor that mediates the pathogenic activity of angiotensin II, represent a major addition to the clinician's armamentarium for the management of hypertension. A solid body of clinical evidence demonstrates that ARBs are effective in the management of hypertension as monotherapy or in combination with other agents. Although comparable to angiotensin-converting enzyme inhibitors and other major classes of antihypertensive agents in the treatment of hypertension, the favorable tolerability profile of ARBs make them an attractive alternative for many patients. Recent evidence suggests that treatment persistence with ARB therapy during a 12-month period is typically higher than with other antihypertensive classes, a finding perhaps driven by fewer treatment-limiting side effects. The combination of clinical efficacy and tolerability should render ARBs as a major treatment alternative for hypertension.
Introduction

Because of its central role in the pathogenesis of cardiovascular disease, the renin-angiotensin-aldosterone system (RAAS) has been a subject of intense research for the past 40 years and an important target for pharmacological intervention in the management of hypertension. This paper provides a brief overview of RAAS function and a review of clinical data related to the use of angiotensin receptor blockers (ARBs) to treat hypertension.

The results of the meta-analysis will be formally presented this week here at the European Society of 2010 Cardiology Congress and were presented early to the media during an afternoon press conference.
Included in the data were 21 studies, including more than 130 000 patients, comparing statins vs placebo controls, and five studies, with approximately 40 000 patients, examining different statin doses. Overall, there was no risk of cancer with statin therapy, and there was no increased risk observed among patients treated with higher statin doses. Numerically, the number of patients who developed cancer was nearly identical in the statin and control arms and in the statin trials comparing higher vs lower doses.
In addition, there was no increased incidence of cancer when investigators analyzed the rates of disease among patients by baseline LDL-cholesterol levels, including levels <77 mg/dL, or by duration of treatment. Similarly, there was no increased risk of any specific types of cancer, such as breast, prostate, bladder, or hematological cancers.

The results of the meta-analysis will be formally presented this week here at the European Society of 2010 Cardiology Congress and were presented early to the media during an afternoon press conference.
Included in the data were 21 studies, including more than 130 000 patients, comparing statins vs placebo controls, and five studies, with approximately 40 000 patients, examining different statin doses. Overall, there was no risk of cancer with statin therapy, and there was no increased risk observed among patients treated with higher statin doses. Numerically, the number of patients who developed cancer was nearly identical in the statin and control arms and in the statin trials comparing higher vs lower doses.
In addition, there was no increased incidence of cancer when investigators analyzed the rates of disease among patients by baseline LDL-cholesterol levels, including levels <77 mg/dL, or by duration of treatment. Similarly, there was no increased risk of any specific types of cancer, such as breast, prostate, bladder, or hematological cancers.

4.

Is Low Vitamin D Associated with Depression in Elders?

Perhaps, but this community-based U.K. study did not explore all possible contributors.

Deficiencies of several vitamins, notably folate and B12, have been associated with depressive symptoms in people aged 65 and older. In this 2005 British national epidemiological household sample, investigators assessed whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with depressed mood in 2070 community-dwelling elders (mean age, 74; 950 men).

The overall prevalence of case-level depressive symptoms was 25.2%. Analyses were adjusted for age, sex, long-term illness, general health status, time of year (to account for sunlight variation), supplement intake, and smoking. Among the 9.8% of this population with clinically meaningful deficiency (25[OH]D levels <10 ng/mL), the prevalence of depressive symptoms was 35.0%, indicating that the prevalence ratio for depressive symptoms was 1.45, compared with nondepressed participants, and that 4.2% of cases with depressive symptoms were potentially attributable to 25(OH)D levels <10 ng/mL.

Comment: Although these researchers examined proxies such as general health status, they did not report patients' sunlight exposure, dietary habits, or serum calcium levels. Because many mechanisms could link low serum vitamin D levels to depressive symptoms, identifying the association is only a first step. Vitamin D deficiencies in older individuals may result from inadequate sunlight exposure due to living at high latitudes or to problems with mobility or pain or both. As the authors note, other variables might include vitamin supplementation and smoking. Furthermore, low vitamin D levels may reflect the presence of hypercalcemia associated with undetected hyperparathyroidism, of which depressive features represent a classic clinical presentation. Clinicians should remember these possible contributors to depression when assessing elders.

— Joel Yager, MD

Published in Journal Watch Psychiatry August 9, 2010

Summary and Comment
Calcium Supplementation Is Associated with Excess Risk for Myocardial Infarction

Marginal-to-moderate bone benefits must be weighed against cardiovascular risks.

Evidence suggests that calcium supplements hasten vascular calcification and increase mortality in patients with kidney failure and raise risk for myocardial infarction (MI) in healthy older women. To further investigate the association between supplemental calcium and adverse cardiovascular events, researchers conducted a meta-analysis of 15 double-blind, randomized trials in which participants (mean age at baseline, >40) received calcium supplements (≥500 mg daily) or placebo.

Patient-level data were available for five trials involving >8000 participants (77% women; median follow-up, 3.6 years). MIs occurred in 143 participants randomized to calcium supplements and 111 randomized to placebo — a significant difference. Calcium supplementation was not associated with excess risk for stroke or death. Analyses of trial-level data, involving 11 studies with nearly 12,000 patients, yielded findings similar to those that were based on patient-level data.

Comment: Calcium supplementation is associated with excess risk for MI. Clinicians should weigh this risk against the marginal-to-modest benefits of calcium supplementation on bone density and fracture risk. Based on current data, the authors estimate that treating 1000 people with calcium supplements for 5 years would prevent only 26 fractures but would cause an additional 14 MIs.

— Paul S. Mueller, MD, MPH, FACP

Published in Journal Watch General Medicine August 31, 2010