• What Happens after People Undergo Direct-to-Consumer Genomic Testing?
• Intestinal Dysbiosis in Very Preterm Infants
• Changing the Surface Microbiota of Cesarean-Delivered Newborns
• Vitamin D Supplementation Doesn't Prevent Colds in Adult Asthma Patients
• Leisure-Time Physical Activity and Cognitive Performance
• 1 in 10 Rural Teens Meet Criteria for Alcohol Use Disorder
• Drinking Coffee Linked to Lower Colorectal Cancer Risk
• Fingolimod Is Not Effective for Primary-Progressive MS
• What this means is Breast Biopsy Study Points to Need for a New "Gold Standard"
• FDA: Powdered Medical Gloves Are Dangerous and Should Be Banned
• The Next Virus to Cause a Pandemic?
• Cost of Insulin Has Nearly Tripled
• Melatonin for Childhood Atopic Dermatitis and Sleep Disturbance
• Triglycerides Again Associated with Cardiovascular Risk in a 22-Year Follow-Up Study
MM: Coming in the Summer of 2016, Mark Drugs Roselle and Deerfield will be offering not only Genomic Testing but the interpretation, explanation, discussion and communication of this information to your health care practitioner (if you so desire). A potential benefit of PharmacoGenomic Testing (PGT) is that if a person is diagnosed and prescribed a medication, PGT can virtually eliminate the possibility of a negative reaction or the clinical failure of that medication. This can save the patient potentially huge amounts of time in receiving adequate treatment, can eliminate many possible failures of therapy, can eliminate many risks of adverse reactions to medications and will ultimately demonstrate very large savings in dollars spent on failed treatments. This last aspect is one of the reasons that many insurance companies are paying for and in several cases, recommending PGT testing.
Ann Intern Med 2016 Mar 1
What Happens after People Undergo Direct-to-Consumer Genomic Testing?
Relatively few people discussed their results with their primary care providers.
We now can learn about our DNA through direct-to-consumer (DTC) personal genomic testing. U.S. researchers assessed the perceptions of 1042 individuals who underwent such testing through either 23andMe or Pathway Genomics. Participants were recruited online and completed baseline surveys and follow-up surveys at 6 months.
Among participants, a higher proportion had annual family income <US$40,000 than ≥$200,000 (16% vs. 12%). Fifty-six percent of respondents planned to discuss the results with their primary care providers (PCPs); however, at 6 months, 65% had not shared their results with any clinician. Among individuals who had not discussed the results with any clinician, a minority (9%) had concerns about the results becoming a part of their medical record and 38% still planned on discussing results. Among participants who shared their results with their PCPs, 35% were very satisfied with the discussions, 46% were somewhat satisfied, and 18% were not at all satisfied.
COMMENT: Whether it is coronary calcium scoring, C-reactive protein measurement, or genomic testing, we have entered into an era where access to information and testing is widely available. Such access potentially has positive effects, including promoting active engagement of patients with the healthcare system. What remains uncertain is whether such genetic information can be translated into improved health outcomes.
CITATION(S): van der Wouden CH et al. Consumer perceptions of interactions with primary care providers after direct-to-consumer personal genomic testing. Ann Intern Med 2016 Mar 1; [e-pub].
(http://dx.doi.org/10.7326/M15-0995)
Burke W and Brown Trinidad S.The deceptive appeal of direct-to-consumer genetics. Ann Intern Med 2016 Mar 1; [e-pub].
(http://dx.doi.org/10.7326/M16-0257)
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MM: Pediatric dysbiosis is a commonly ignored condition that may be a much greater global problem than typically recognized. This may have several possible sources. C-section babies are denied the opportunity to orally bet their mom's normal flora during birth as they are removed from a relatively sterile field as compared to the birth canal. These babies require breast feeding to secondarily obtain these healthy microorganisms that are necessary to balance their systems. Multiple vaginal births will frequently see the second or other later multiparous births experience dysbiosis due to a sort of "cleansing" of the birth canal by the first born.Children with recurrent ear problems are typically administered recurrent courses of antibiotics without (historically) typically receiving probiotics to counter the ensuing dysbiosis. These are just a couple of the scenarios that commonly occur. The bottom line is that breast feeding and probiotic administration are two simple ways to ameliorate these dysbiosis problems and unfortunately not enough people (physicians and lay) are aware of these remedies.
Lancet 2016 Mar 8
Intestinal Dysbiosis in Very Preterm Infants
An abnormal intestinal microbiome may precede necrotizing enterocolitis in very preterm babies.
Necrotizing enterocolitis is a common and devastating complication of prematurity, with high mortality and very high morbidity for survivors. While prematurity and formula feeding are known to be important risk factors for the disease, its infectious nature has raised questions about whether postnatal acquisition of pathogenic bacteria contributes to its pathogenesis.
In this multicenter study, researchers prospectively collected serial stool samples for microbial DNA analysis from very low birth weight infants (≤1500 g) at risk for necrotizing enterocolitis. DNA was analyzed from samples collected the day of admission to the neonatal intensive care unit (NICU) through the day before diagnosis of necrotizing enterocolitis or age 60 days.
In the primary cohort of 122 infants from a single NICU, 28 developed necrotizing enterocolitis and the remaining 94 served as controls. The rate of change of stool microbial patterns differed between the two groups, with cases, relative to controls, showing significant increases in Gammaproteobacteria and significant decreases in strictly anaerobic bacteria, especially Negativicutes, after the first month of life. Infants born at less than 27 week's gestation accounted for most of the differences between groups. These findings were confirmed in a secondary cohort from two different NICUs that included a total of 18 cases and 22 controls.
COMMENT: Preterm babies who develop necrotizing enterocolitis are more likely to have an associated intestinal “dysbiosis,” with a predominance of Gammaproteobacteria (pathogenic gram-negative bacilli such as Escherichia coli, Enterobacter, and Klebsiella) and low levels of strict anaerobic bacteria (Negativicutes). Learning how best to support a favorable microbiome environment may help improve outcomes for infants born at less than 27 weeks' gestation.
Dr. Steinhorn is Professor and Chair of Pediatrics, University of California Davis Medical Center, Sacramento.
CITATION(S): Warner BB et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: A prospective case-control study. Lancet 2016 Mar 8; [e-pub]. (http://dx.doi.org/10.1016/S0140-6736(16)00081-7)
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Nat Med 2016 Mar; 22:250
Changing the Surface Microbiota of Cesarean-Delivered Newborns
Applying vaginal fluids to infants soon after birth by C-section resulted in a surface microbiota resembling that seen in babies delivered vaginally.
Epidemiologic studies have suggested that the increasing use of cesarean (C)-section may be associated with increased risks for asthma, allergies, and immune deficiencies. Babies born by C-section have been found to have a microbiota that is enriched in skin organisms, whereas those delivered vaginally harbor bacterial communities resembling the maternal vagina. These differences could have an effect on subsequent immune development.
To assess whether the skin microbiome of C-section–delivered infants could be altered by vaginal microbial transfer, investigators conducted a pilot study in which 4 of 11 babies born by C-section were swabbed at their mouth, face, and body within 2 minutes of birth with gauze that had been soaked in their mothers' vaginal fluids. Subsequent oral, anal, and skin samples were obtained at six time points during the first month of life, and were compared with those from seven babies delivered vaginally and from the seven others delivered by C-section who were not swabbed with vaginal fluid. The microbiome compositions of the babies and the maternal vaginas were characterized by sequencing the V4 region of 16S rRNA gene.
The microbiomes of the C-section–delivered infants exposed to vaginal fluids resembled those of vaginally-delivered infants and were more similar to the maternal vaginal microbiomes than those of unexposed C-section infants. Anal samples from vaginally-delivered and C-section swabbed infants showed an early enrichment of Lactobacillus followed by a bloom of Bacteroides, which was not observed in C-section–delivered newborns who were not exposed to vaginal fluids.
COMMENT: This paper demonstrates that a relatively simple application of vaginal fluids could at least partially restore the surface microbiota of newborns delivered by C-section. However, the long-term effect of this intervention remains unknown. As the authors note, this small study represents a proof of principle that will require further study.
CITATION(S): Dominguez-Bello MG et al. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 2016 Mar; 22:250. (http://dx.doi.org/10.1038/nm.4039)
http://www.ncbi.nlm.nih.gov/pubmed/26828196?access_num=26828196&link_
type=MED&dopt=Abstract
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MM: These results are directly in conflict to those that we have experienced in our practice. We have seen consistently that those who increase their 25-OH-D levels to a 60-80ng/ml range appear to have less frequent and less severe episodes of cold, flu and asthmatic attacks. I do not know if a critical goal is 60-80ng/ml that makes this difference or other health components that contribute to an overall better state. The bottom line is that we see consistent benefits to higher blood levels of vitamin D compared to the lower ranges.
Am J Respir Crit Care Med 2016 Mar 15; 193:634
Vitamin D Supplementation Doesn't Prevent Colds in Adult Asthma Patients
Vitamin D supplementation seems to be a cure waiting for a disease.
Vitamin D deficiency has been linked to asthma and to susceptibility for acute respiratory tract infections, but vitamin D supplementation has yielded inconsistent benefit. In a previously published trial, 408 adult patients with mild-to-moderate asthma and serum 25-hydroxyvitamin D (25[OH]D) levels <30 ng/mL received placebo or cholecalciferol (vitamin D3; 100,000 IU initial dose, then 4000 IU daily) for 28 weeks while inhaled corticosteroids were tapered. Time to first asthma treatment failure and incidence of exacerbations were similar in the two groups (NEJM JW Gen Med Jul 1 2014 and JAMA 2014; 311:2083). Now, in a prospectively planned, secondary analysis, the investigators evaluated whether vitamin D3 supplementation lowers the incidence and severity of colds.
Average posttreatment 25(OH)D level in the vitamin D3 group was 41.9 ng/mL. Half of participants experienced at least one self-reported cold; no difference was found between groups in number of colds or in the primary endpoint of cold-symptom severity (measured by validated questionnaires). Among black patients, those who received vitamin D3 were significantly more likely than those who received placebo to experience cold symptoms.
COMMENT: Vitamin D supplementation seems to be a cure waiting for a disease. Although some studies suggest that vitamin D3 supplementation benefits children, it shows no benefit for preventing asthma exacerbations or cold symptoms in adults with mild-to-moderate asthma. On the contrary, the authors speculate that supplementation might have made some otherwise asymptomatic colds symptomatic by reconstituting the inflammatory response.
CITATION(S): Denlinger LC et al. Vitamin D supplementation and the risk of colds in patients with asthma. Am J Respir Crit Care Med 2016 Mar 15; 193:634. (http://dx.doi.org/10.1164/rccm.201506-1169OC)
http://www.ncbi.nlm.nih.gov/pubmed/26540136?access_num=26540136&link_
type=MED&dopt=Abstract
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MM: This is another example of, "If you don't use it, you lose it". The only difference is that this looks at a crossover of inactivity effecting cognitive function and speed of mental processing. These results may be a result of decreased blood flow to the brain due to lower cardiac output or it may be a result of the normal detoxifying process that the body has with increased physical activity. Whatever the actual etiology, the bottom line is that being sedentary does not just cause the body to be sluggish but the brain as well.
Neurology 2016 Mar 23
Leisure-Time Physical Activity and Cognitive Performance
Low levels of leisure-time physical activity may be associated with lower scores in specific cognitive domains.
To examine the effect of leisure-time physical activity on cognitive performance over time, researchers enrolled 1228 adults (mean age, 70.6 years), of whom 876 participated in a 5-year follow-up evaluation. Leisure-time physical activity was categorized into no/light activity versus moderate/heavy activity based on metabolic-equivalent scores calculated from questionnaire data. Neuropsychological tests evaluated processing speed, semantic memory, episodic memory, and executive function. The effect of leisure-time physical activity on cognitive performance was determined after first adjusting for sociodemographics, then cardiovascular risk factors, and finally white matter hyperintensity volume, cerebral volume, and presence of silent brain infarcts on magnetic resonance imaging (MRI).
In the total sample, no/light activity was associated with worse scores on processing speed, executive function, and semantic memory at baseline after adjustment for sociodemographics but not after adjustment for vascular risk factors and MRI findings. At follow-up, no/light activity was associated with worse scores on processing speed after adjustment for sociodemographics and vascular risk factors but not after adjustment for MRI findings.
In participants who were cognitively unimpaired at baseline, no/light activity was associated with worse scores on processing speed at baseline and follow-up evaluation after adjustment for sociodemographics. No/light activity also was associated with worse scores on episodic memory at follow-up evaluation after adjustment for sociodemographics, vascular risk factors, and MRI findings.
COMMENT: Low levels of leisure-time physical activities may worsen scores on processing speed and episodic memory, particularly in older adults who are cognitively unimpaired. Leisure-time physical activity of moderate/heavy intensity may be important in optimizing cognitive performance, although the exact frequency and duration of these activities still need to be determined.
CITATION(S): Willey JZ et al. Leisure-time physical activity associates with cognitive decline: The Northern Manhattan Study. Neurology 2016 Mar 23; [e-pub]. (http://dx.doi.org/10.1212/WNL.0000000000002582)
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1 in 10 Rural Teens Meet Criteria for Alcohol Use Disorder
By Amy Orciari Herman, Edited by Susan Sadoughi, MD, and Richard Saitz, MD, MPH, FACP, FASAM
Roughly 10% of adolescents aged 15 and older meet DSM-5 criteria for alcohol use disorder, a study in the Journal of Pediatrics finds.
Nearly 1200 adolescents aged 12–20 in rural Pennsylvania primary care practices completed alcohol use assessments. DSM-5 criteria for alcohol use disorder were met by 1.9% of those aged 12–14 years and roughly 10% of those aged 15–17 or 18–20. For those aged 12–17, consuming at least one standard drink on 3 or more days in the past year was most predictive of a diagnosis of alcohol use disorder. For the oldest participants, having 12 or more drinking days in the past year was most predictive.
For a "simplified approach to alcohol screening," the authors advise clinicians to start by asking adolescents about their frequency of alcohol use in the past year. Those who screen positive (based on the above frequency criteria) would then undergo a full evaluation for alcohol use disorder.
http://www.jpeds.com/article/S0022-3476(16)00269-9/pdf
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MM: A unique aspect of this study is that it does not examine caffeine. Rather, it looks at "coffee". I like the possible conclusion that coffee may have an effect on the microbiome as we know that a dysbiotic condition of the colon can contribute to colitis and possible colon cancer. I think that moderate coffee consumption may be a good thing in general like so many other things done in moderation.
Drinking Coffee Linked to Lower Colorectal Cancer Risk
By Kelly Young,, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Regular coffee drinkers may have a reduced risk for developing colorectal cancer, according to a case-control study in Cancer Epidemiology, Biomarkers & Prevention.
Researchers assessed coffee consumption in 5100 people with colorectal cancer in Israel and 4100 controls free of colorectal cancer. After multivariable adjustment, any coffee consumption was tied to a 26% reduced risk for incident colorectal cancer, compared with no coffee intake. The risk was lowest in the highest consumption group (more than 2.5 cups a day). Benefits were seen with both regular and decaf coffee.
The authors speculate that coffee's components could affect motility and fecal output, microbiome composition, and inflammation. They conclude: "The health risks of coffee consumption are low, but additional evidence is warranted before advocating for coffee consumption as a nutraceutical approach to reduce the risk of colorectal cancer."
http://cebp.aacrjournals.org/content/25/4/634
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MM: I find that it is just as important to know what does "not" work a it is to know what "does" work for a condition. That is why this article is so valuable. Treatments such as high dose vitamin D3 and Low Dose Naltrexone and High Dose Biotin have demonstrated amazing effectiveness for MS of a variety of categories and show very few potential adverse reactions in the patients who use them. Unfortunately, since these approaches are not widely marketed to physicians by major drug company sales forces they are frequently ignored or used as a "last resort", rather than as a primary treatment.
Lancet 2016 Mar 12; 387:1075
Fingolimod Is Not Effective for Primary-Progressive MS
A randomized trial provides definitive evidence.
Most patients with multiple sclerosis (MS) present with its relapsing form, whereas about 10% to 15% exhibit progressive neurological disability with or without minimal relapse activity – known as primary-progressive MS. Although several licensed therapies can modify the course of relapsing MS, there are currently none for primary-progressive disease.
Fingolimod, an oral sphingosine 1-phosphate receptor modulator effective in relapsing MS, was studied in 970 patients with primary-progressive MS in a multicenter, randomized, double-blind, parallel-group study funded by the manufacturer. Patients between ages 25 and 65 received daily fingolimod or placebo and were monitored for at least 3 years.
The primary outcome was confirmed disability progression (CDP), defined as a composite endpoint based on a change — confirmed 3 months later — in the rater-based Expanded Disability Status Scale, 25-foot timed walk, or 9-hole peg test of upper limb function. There was no difference in outcome incidence between fingolimod and placebo (hazard ratio, 0.95; 95% confidence interval, 0.8–1.12; P=0.544). There was also no difference in brain-volume loss on magnetic resonance imaging between groups.
COMMENT: This well-powered, well-designed, randomized, controlled trial definitively shows that oral fingolimod is not effective in reducing the risk for disability progression in primary-progressive MS. These results, although disappointing, are not entirely unexpected, given several other negative trials of anti-inflammatory therapies that are effective in relapsing-remitting MS. Discovering the mechanisms driving the pathophysiology of progressive MS is a top research priority. Therapeutic approaches specific for progressive MS will likely be needed to modify the insidious, neurodegenerative aspect of the disease.
Dr. Gelfand is Assistant Professor of Clinical Neurology, MS and Neuroinflammation Center, University of California, San Francisco.
CITATION(S): Lublin F et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): A phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2016 Mar 12; 387:1075
(http://dx.doi.org/10.1016/S0140-6736(15)01314-8)
http://www.ncbi.nlm.nih.gov/pubmed/26827074?access_num=26827074&link_
type=MED&dopt=Abstract
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What this means is Breast Biopsy Study Points to Need for a New "Gold Standard"
By Joe Elia, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
Breast biopsy findings, the gold standard for diagnosis, can vary widely among pathologists, especially with atypia and ductal carcinoma in situ (DCIS), according to an Annals of Internal Medicine study.
The B-Path Study sent single slides from 240 biopsies of U.S. women aged 50–59 to over 100 pathologists. Their findings were compared with the consensus diagnosis of a panel of three experts.
Individual pathologists' findings for invasive cancer and benign tissue without atypia were more than 97% concordant with the expert panel. However, DCIS findings were 70% concordant, and findings of atypia were only 40% concordant; in both of those cases the error was typically in the direction of a more serious finding.
The authors call for efforts to reduce diagnostic variability, and editorialists observe that "accuracy remains limited by the current (hopefully short-lived) inability of medical science to distinguish innocuous cancer cases from dangerous ones."
http://annals.org/article.aspx?articleid=2505396
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FDA: Powdered Medical Gloves Are Dangerous and Should Be Banned
By Kristin J. Kelley, Edited by David G. Fairchild, MD, MPH, and Jaye Elizabeth Hefner, MD
The FDA has announced a plan to ban most powdered medical gloves (e.g., surgical gloves, patient exam gloves, and powder used to lubricate surgical gloves). Powdered surgical gloves are easier to put on and take off, but they pose a substantial risk to anyone exposed to them, the agency warns.
Aerosolized glove powder on latex gloves can lead to respiratory allergic reactions. Potential risks from powdered synthetic gloves include postsurgical adhesions, severe airway inflammation, and wound inflammation.
The ban, which would mean taking the gloves off the market, would not apply to non-powdered patient examination or surgeon gloves. The proposal marks only the second time in history the FDA has recommended banning a medical supply, the Associated Press reports. (The first was back in 1983, when it banned fake hair implants.)
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491466.htm
http://www.usnews.com/news/business/articles/2016-03-21/fda-moves-to-ban-powdered-surgical-gloves
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MM: Whenever I read an article like this I start to think that maybe shows like "The Walking Dead" are not as whimsical as their graphic novel origins suggest.
Proc Natl Acad Sci U S A 2016 Mar 15; 113:3048
The Next Virus to Cause a Pandemic?
Researchers have identified a novel bat-derived coronavirus that can infect human cells.
Outbreaks of severe acute respiratory syndrome (SARS) and the Middle Eastern respiratory syndrome (MERS) were both due to a cross-species spread of animal coronaviruses. Given the concern that other animal coronaviruses might be able to cross species, researchers have now used reverse genetic techniques to study a bat coronavirus, WIV1-CoV, that has been shown to infect human cells.
Studies of WIV1-CoV and a mouse-adapted chimeric variant, WIV1-MA15, showed that both readily infected primary human airway epithelial cells. These two viruses could not efficiently infect wild-type mice, but could cause infection and disease in chimeric mice that expressed the human angiotensin-converting enzyme 2 receptor in lung tissue, although not as efficiently as the SARS coronavirus (SARS-CoV). Monoclonal antibodies selected against SARS-CoV protected mice against both SARS-CoV and WIV1-CoV, although a candidate SARS-CoV vaccine showed no protective efficacy.
COMMENT: This work shows that there is at least one more animal coronavirus that could cause human disease. Whereas WIV1-CoV may never cause a human pandemic, these findings also suggest that to prevent future pandemics, it could be worthwhile to perform systematic screening for other nonhuman viruses that can infect human cells.
CITATION(S):Menachery VD et al. SARS-like WIV1-CoV poised for human emergence. Proc Natl Acad Sci U S A 2016 Mar 15; 113:3048.
(http://dx.doi.org/10.1073/pnas.1517719113)
http://www.pnas.org/content/113/11/3048?ijkey=419a4f2b72767b7d18c71873717
e54d7ac1f8d1a&keytype2=tf_ipsecsha
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Cost of Insulin Has Nearly Tripled
By Kelly Young, Edited by David G. Fairchild, MD, MPH
The price of insulin nearly tripled over the course of a decade, according to a JAMA research letter.
Researchers surveyed 28,000 people with diabetes from 2002 through 2013. In 2002, each patient spent an estimated $231 for insulin, and by 2013, this amount increased to $736 (costs were adjusted for inflation). The annual quantity of insulin taken per person increased from 171 to 206 mL, and the mean price per milliliter of insulin increased by 197% during this period.
In comparison, the mean price of dipeptidyl peptidase-4 inhibitors rose by 34%, while the mean price of metformin fell by 93%.
The authors conclude: "Significant changes in mean price of insulin, relative to comparator therapies, suggest a need to reassess the effectiveness and cost-effectiveness of alternative antihyperglycemic therapies."
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MM: I am frequently asked about atopic dermatitis in young children. This is an interesting and seemingly safe approach that may be added to my clinical arsenal.
JAMA Pediatr 2016 Jan 1; 170:35
Melatonin for Childhood Atopic Dermatitis and Sleep Disturbance
A well-conducted randomized, double-blind trial suggests that melatonin may improve both.
Sleep disturbance is common in patients with atopic dermatitis (AD), but effective management is lacking. Reduced nocturnal melatonin has been found to be associated with sleep disturbance and greater AD severity.
Investigators in a Taiwanese tertiary care hospital performed a randomized, double-blind, placebo-controlled, crossover study in children with AD (age, 1–18 years, with AD on >5% body surface area), and sleep problems >3 days/week over 3 months. Children with sleep disorders or taking insomnia or antidepressant medications were excluded. All underwent a 2-week preparation using a sleep diary, a fixed sleep schedule, and caffeine avoidance. Children were then randomized to either 3-mg melatonin or placebo tablets orally once daily, for 4 weeks. After a 2-week washout, the groups switched treatments. AD skin-care regimens were unchanged. On the first and last day of each treatment, blood/urine samples were collected, questionnaires given, and the scoring atopic dermatitis (SCORAD) index was assessed by the same blinded physician. Sleep was assessed by actigraphy in all, and polysomnography in a subgroup of patients.
Compared to placebo, melatonin decreased the SCORAD index from a mean of 49 to 40 (P< 0.001), and sleep onset latency shortened by 21 minutes. More patients reported AD and sleep improvement with melatonin than with placebo. There was no significant difference in sleep stages and limb movement with melatonin versus placebo. No adverse event was reported during the study.
COMMENT: Sleep disturbance has far-reaching consequences for children and families. This small but carefully conducted study suggests that melatonin may improve not only sleep, but also AD severity. Further studies are needed to establish safety, efficacy, and optimum dosing.
CITATION(S): Chang Y-S et al. Melatonin supplementation for children with atopic dermatitis and sleep disturbance: A randomized clinical trial. JAMA Pediatr 2016 Jan 1; 170:35. (http://dx.doi.org/10.1001/jamapediatrics.2015.3092)
http://www.ncbi.nlm.nih.gov/pubmed/26569624?access_num=26569624&link_
type=MED&dopt=Abstract
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Circ Cardiovasc Qual Outcomes 2016 Mar; 9:100
Triglycerides again Associated with Cardiovascular Risk in a 22-Year Follow-Up Study
But does lowering triglycerides improve risk?
The role of high levels of triglycerides in cardiovascular disease remains poorly understood. Now, investigators have reported long-term mortality data on the 15,355 patients initially screened for the placebo-controlled Bezafibrate Infarction Prevention (BIP) trial, which enrolled 3122 patients with coronary heart disease and found a statistically nonsignificant 9.4% reduction in the primary endpoint (fatal and nonfatal myocardial infarction plus sudden death) with bezafibrate, a triglyceride-lowering drug (Circulation 2000; 102:21).
At follow-up (median, 22.8 years), successively higher baseline fasting triglyceride levels were linked to successively higher age- and sex-adjusted mortality rates, even in multivariate analysis controlling for multiple potential confounders. Each logarithmic unit increase in triglycerides was associated with a 26% increase in age- and sex-adjusted all-cause mortality. Patients with the highest triglyceride levels (≥500 mg/dL) had a significantly lower 22-year survival rate than those with “low-normal” levels of <100 mg/dL (25% vs. 41%). Even high-normal triglyceride levels (100–149 mg/dL) were associated with increased mortality.
COMMENT: Some limitations of this study are the lack of adjudication of deaths and the lack of information during follow-up about lipid values, medication use, and comorbidities such as diabetes. In addition, this study needs to be put into the context of present-day clinical care. When the trial was conducted, the standard of care was to provide lipid management only to patients with considerably higher LDL cholesterol levels. The authors point out that >90% of the patients in the BIP trial were receiving no lipid-modifying medications at enrollment. We currently do not know whether triglyceride elevations will hold similar predictive value in patients whose LDL cholesterol levels are optimally controlled. And we must always remember: Simply because something may be a cardiovascular risk factor, altering it pharmacologically doesn't always lower risk.
CITATION(S): Klempfner R et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: Twenty-two-year follow-up of the Bezafibrate Infarction Prevention study and registry. Circ Cardiovasc Qual Outcomes 2016 Mar; 9:100.
(http://dx.doi.org/10.1161/CIRCOUTCOMES.115.002104)
http://circoutcomes.ahajournals.org/content/9/2/100?ijkey=78913d0579fabd6
f0b4409b22445a9e7053e49da&keytype2=tf_ipsecsha
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