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Medika A shelf on health
sunday, july 21, 2013
Gara-gara Diare, 50.000 Bocah Indonesia Meninggal http://bisnis.com/gara-gara-diare-50000-bocah-indonesia-meninggal Fatkhul Maskur 130411_bayiedwinsihombing.jpg
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JAKARTA - Pneumonia dan diare merupakan penyakit infeksi yang menjadi penyebab utama kematian bayi di Indonesia dengan lebih dari 50 ribu balita meninggal per tahun akibat penyakit tersebut.
2014 (28)
"Salah satu kabupaten dengan angka kematian anak balita (Akaba) tertinggi di Indonesia ada
t 2013 (82)
di Kabupaten Jayawijaya, Provinsi Papua, di mana pada 2011 diperkirakan Akaba sebanyak
December (6)
122 per 1.000 kelahiran hidup," kata Direktur Bina Kesehatan Anak Jane Soepardi dalam
November (4)
temu media di Jakarta, Jumat (19/7/2013).
October (12)
Daerah Indonesia Timur disebut Jane merupakan daerah dengan kematian anak dan balita
September (3)
yang cukup tertinggi terutama bagi masyarakat di daerah terpencil, perbatasan dan
August (3)
kepulauan yang sulit dijangkau oleh petugas kesehatan.
t July (6) Gara-gara Diare, 50.000 Bocah Indonesia Meninggal Scientists find how 'obesity gene' makes people fa... Study Finds Benefits in Delaying Severing of Umbil... 21 reasons why you should have sex.. tonight! More Dry Eyes in the House Hypertriglyceridemia: its etiology, effects and tr... June (13) May (11)
Padahal pengobatan seharusnya sederhana dan murah namun akses yang sulit menyebabkan masih banyak kematian anak dan balita akibat kedua penyakit ini. Studi mortalitas 2013 menyatakan penyebab kematian anak balita terbesar di Jayawijaya adalah pneumonia (56%) dan diare (20%). Pengobatan bagi pneumonia seharusnya mudah yaitu dengan memberikan kotrimoksazol untuk pengobatan pneumonia serta memberikan oralit dan tablet zinc untuk pengobatan diare dan untuk pencegahan dapat dilakukan dengan pemberian ASI ekslusif bagi bayi 0-6 bulan serta membiasakan untuk hidup sehat seperti mencuci tangan memakai sabun. Sementara itu, untuk menjangkau anak-anak di daerah terpencil, Kementerian Kesehatan bekerjasama dengan beberapa lembaga swadaya masyarakat (LSM) melakukan uji coba program Manajemen Terpadu Balita Sakit (MTBS) di enam kabupaten di lima provinsi yaitu Aceh, Kalimantan Timur, NTT dan Papua).
April (7)
"MTBS berbasis masyarakat ini terbukti berhasil, banyak anak-anak yang tidak dapat
March (7)
menjangkau tenaga kesehatan dapat ditolong oleh kader-kader ini," kata Jane.
February (6) January (4) 2012 (100)
Pada 2011, program MTBS-M di Jayawijaya itu melatih 34 kader kesehatan yang tersebar di lima puskesmas dan selama Januari-Desember 2012, pata kader tersebut menangani 1.144 kasus anak balita sakit (360 kasus pneumonia dan 255 kasus diare).
2011 (87)
"Program ini berhasil menjangkau anak balita sakit di wilayah yang sangat sulit. Tanpa
2010 (18)
dedikasi para kader dan kerjasama yang baik dengan tenaga kesehatan, sebagian besar anak
2009 (2)
balita di wilayah sulit ini tidak mendapatkan akses ke layanan pengobatan," papar Jane.
2008 (22) 2007 (12)
Namun kesuksesan program MTBS itu diakui Jane masih belum mendapatkan dukungan dari beberapa pemerintah daerah yang khawatir mengenai bahaya kader mengobati anak secara langsung.
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Padahal dukungan pemda itu disebut Jane sangat penting bagi kelangsungan program yang disebutnya diawasi ketat oleh tenaga kesehatan dari puskesmas setempat yang secara rutin akan melakukan evaluasi terhadap para kader. Posted by dewi darmawati at 8:55 PM
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tuesday, july 16, 2013
Scientists find how 'obesity gene' makes people fat http://uk.reuters.com/article/2013/07/15/us-obesity-gene-idUKBRE96E0KB20130715 Ben Hirschler
(Reuters) - Scientists have unraveled how a gene long associated with obesity makes people fat by triggering increased hunger, opening up potential new ways to fight a growing global health problem.
A common variation in the FTO gene affects one in six of the population, making them 70 percent more likely to become obese - but until now experts did not know why. Using a series of tests, a British-led research team said they had found that people with the variation not only had higher levels of the "hunger hormone" ghrelin in their blood but also increased sensitivity to the chemical in their brains. "It's a double hit," said Rachel Batterham from University College London, who led the study, which was published in the Journal of Clinical Investigation on Monday. The discovery follows studies of blood samples from people after meals, combined with functional magnetic resonance imaging of volunteers' brains and cell-based studies looking at ghrelin production at a molecular level. Batterham said the work provided new insights and possible new leads for treatment, since some experimental drugs are known to suppress ghrelin and could be particularly effective if targeted at patients with the obesity-risk variant of the gene. Previous research has also shown that ghrelin can be reduced by eating a high-protein diet. Steve Bloom of Imperial College London, who was not involved in the study, said the FTO gene only explained a small part of the obesity epidemic but the latest discovery was "an important step forward" in unraveling the various factors involved. The prevalence of obesity is increasing worldwide at an alarming rate and both developed and developing countries are affected. Obesity is a major risk factor for diabetes, heart disease and certain cancers. At least 2.8 million adults die each year as a result of being overweight or obese and more than 40 million children under the age of five were overweight in 2011, according to the World Health Organization. Developing effective obesity drugs has been a challenge for drugmakers, although some new medicines are now coming through. After a gap of more than a decade, two new obesity drugs - Vivus Inc's Qsymia and Arena Pharmaceuticals Inc's Belviq - were approved by the U.S. Food and Drug Administration last year. Belviq's launch was delayed, however, pending a final classification on its risk of abuse and Qsymia's sales have been disappointing, triggering fierce criticism from Vivus's largest shareholder. (Editing by Sophie Walker) Posted by dewi darmawati at 2:51 AM
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monday, july 15, 2013
Study Finds Benefits in Delaying Severing of Umbilical Cord http://www.nytimes.com/2013/07/11/health/study-endorses-later-severing-of-umbilicalcord.html?src=me&ref=general&_r=0 CATHERINE SAINT LOUIS
Newborns with later clamping had higher hemoglobin levels 24 to 48 hours postpartum and were less likely to be iron-deficient three to six months after birth, the study determined. In most hospital delivery rooms, doctors routinely clamp and sever the umbilical cord less than a minute after an infant’s birth, a practice thought to reduce the risk of maternal hemorrhaging. But a new analysis has found that delaying clamping for at least a minute after birth, which allows more time for blood to move from the placenta, significantly improves iron stores and hemoglobin levels in newborns and does not increase the risks to mothers. Doctors usually clamp the umbilical cord in two locations, near the infant’s navel and then farther along the cord, then cut it between the clamps. The timing of the procedure has been controversial for years, and the new analysis adds to a substantial body of evidence suggesting that clamping often occurs too quickly after delivery. The new paper, published on Wednesday in The Cochrane Database of Systematic Reviews, may change minds, though perhaps not immediately. “I suspect we’ll have more and more delayed cord clamping,” said Dr. Jeffrey Ecker, the chair of committee on obstetrics practice for the American College of Obstetricians and Gynecologists. Newborns with later clamping had higher hemoglobin levels 24 to 48 hours postpartum and were less likely to be iron-deficient three to six months after birth, compared with term babies who had early cord clamping, the analysis found. Birth weight also was significantly higher on average in the late clamping group, in part because babies received more blood from their mothers. Delayed clamping did not increase the risk of severe postpartum hemorrhage, blood loss or reduced hemoglobin levels in mothers, the analysis found. “It’s a persuasive finding,” said Dr. Ecker. “It’s tough not to think that delayed cord clamping, including better iron stores and more hemoglobin, is a good thing.” The World Health Organization recommends clamping of the cord after one to three minutes because it “improves the iron status of the infant.” Occasionally delayed clamping can lead to jaundice in infants, caused by liver trouble or an excessive loss of red blood cells, and so the W.H.O. advises that access to therapy for jaundice be taken into consideration. By contrast, in December a committee opinion by the American College of Obstetricians and Gynecologists reviewed much of the same evidence as the new analysis but found it “insufficient to confirm or refute the potential for benefits from delayed umbilical cord clamping in term infants, especially in settings with rich resources.” The committee cited the risks of jaundice and the relative infrequency of iron deficiency in the United States as reasons for not changing longstanding practice. But Dr. Tonse Raju, a neonatologist and an author of the guidelines, said he personally favored delayed cord clamping, even more so after this “very strong paper.” The new report assessed data from 15 randomized trials involving 3,911 women and infant pairs. Eileen Hutton, a midwife who teaches obstetrics at McMaster University in Ontario and published a systematic review on cord clamping, called the report “comprehensive and well done” but said she felt the conclusion was “weakly worded,” considering the sum of evidence on the benefits of delayed cord clamping for neonates. “The implications are huge,” Dr. Hutton said. “We are talking about depriving babies of 30 to 40 percent of their blood at birth — and just because we’ve learned a practice that’s bad.” Said Dr. Raju, a medical officer at the National Institute of Child Health and Human Development: “It’s a good chunk of blood the baby is going to get, if you wait a minute and a half or two minutes. They need that extra amount of blood to fill the lungs.” Healthy babies manage to compensate if they do not get the blood from the cord, he said, but researchers do not know how. American doctors hesitate to recommend delaying cord clamping universally, Dr. Raju said, because there can be situations in which early clamping is required — if an infant requires resuscitation, for example, or aspirates meconium, or infant stool. The new analysis also found a 2 percent increase in jaundice among babies who got delayed cord clamping, compared with those who did not. Dr. Raju noted that the risk, although slight, increases the need for follow-up testing three to five days postpartum. Susan McDonald, the lead author of the Cochrane review and a professor of midwifery at La Trobe University in Melbourne, Australia, said, “In terms of a healthy start for a baby, one thing we can do by delaying cord clamping is boost their iron stores for a little bit longer.” The new analysis did not include many women who had Caesarean sections, some experts noted. “We don’t have enough information on the effects of delayed cord clamping for someone undergoing a Caesarean delivery in terms of postpartum hemorrhage,” said Dr. Cynthia Gyamfi-Bannerman, medical director of the perinatal clinic at Columbia University. “Waiting 30 or 60 seconds in a vaginal delivery in a low-risk patient is probably something we could do and wouldn’t have maternal consequences, but in a caesarean delivery, you’re cutting into a pregnant uterus that has a huge amount of blood.” In some scenarios, “there’s an increased risk of postpartum hemorrhage.” Dr. McDonald acknowledged that the review did not include data on the long-term neurological outcomes for babies. “What will sway A.C.O.G. are a couple of studies in progress showing a potential long-term neurological benefit,” Dr. Raju said. Improved iron stores in theory could help reduce the risk of learning deficiencies and cognitive delay in children, which have been linked to irondeficiency anemia in school-age children.
Posted by dewi darmawati at 1:04 PM
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thursday, july 11, 2013
21 reasons why you should have sex.. tonight! http://www.mirror.co.uk/lifestyle/health/21-reasons-you-should-sex-2043200
Forget anti-wrinkle creams, research claims SEX can make you look seven years younger - but that's not the only benefit
Partner “not in the mood” again? Then it might be worth sharing the following to change their mind! According to the latest studies, regular sex – that’s one to two lovemaking sessions per week – can provide some incredible boosts to your health and wellbeing. 1 Look younger Last week, Dr David Weeks, clinical neuropsychologist at the Royal Edinburgh Hospital, revealed to a psychology conference that his extensive research had found older men and women with an active love life looked five to seven years younger than their actual age. But you don’t have to be at it every night to enjoy youth-enhancing effects! In fact, during his 10-year study, Weeks found quality was as important as quantity, with the anti-ageing benefits stronger if the sex was classed as “loving”. 2 Boost your fertility This will sound like music to most men’s ears – studies have found that the more often you make love, the better quality your sperm will be. Semen health was found to be best when sex had last occurred less than two days before the sperm was tested and was greatly decreased after 10 days of abstinence. If you’re trying for a baby, keep sperm fresh and in tip-top shape by having sex at least twice a week, and not only around the time of the woman’s ovulation. Frequent sex has also been found to help balance a woman’s hormones and regulate her periods, which can further boost chances of conceiving. 3 Fight colds and flu Having sex once or twice a week has been found to raise your body’s levels of an antibody called immunoglobulin A, or IgA, which can protect you from colds and flu. One study found people who have sex more than once a week have 30% higher levels of IgA than those who abstain. 4 Disease-proof your body Having high levels of the natural steroid DHEA, known as “the anti-ageing hormone”, is believed to be key to keeping your body fitter for longer. During sex, DHEA is secreted throughout the body, and after an orgasm, the level in the bloodstream soars to five times its normal amount. 5 Lengthen your life A study carried out in Australia found people who climaxed at least three times a week had a 50% lower chance of dying for any medical reason than those who only climaxed once a month. 6 Shift your middle-age spread and keep fit Thirty minutes of vigorous sex burns up to 100 calories, which is the same as a small glass of wine. And if you have moderately active sex twice a week, you’ll burn an extra 5,000 calories a year! Varying your positions is also a great, fun way to tone different muscle groups and keep limbs lean and flexible. 7 Ease those nasty period cramps Many women say period pain diminishes if they do the deed during a cramp attack. One theory why is that muscle contractions that occur when you reach peak levels of excitement relieve tension in the muscles of your uterus – the ones that cause menstrual cramps – therefore easing the pain. 8 Helps lower your risk of incontinence Good sex is a great workout for a woman’s pelvic floor muscles – the muscles that control orgasms and also stem the flow of urine, reducing leakage and incontinence. Pregnancy and the menopause can weaken these muscles significantly, but the stronger they are, the lower your risk of developing stress incontinence and prolapse later. And let’s face it, sex is far more enjoyable than the chore of doing pelvic floor exercises on your own! 9 Prevent a heart attack Lots of studies have found that regular sex can ward off heart attacks, not bring them on as it was once feared. One study at Queen’s University Belfast found that having sex three times a week could halve your risk of having a heart attack or stroke. Another study in Israel found that women who had two orgasms a week were up to 30% less likely to have heart disease than those who did not enjoy sex or didn’t have an orgasm. 10 Increase your attractiveness to others High sexual activity makes the body release more pheromones, chemicals that enhance your appeal to the opposite sex. This is why the more sex you have with your partner, the stronger your desire will be to have sex with them again. 11 Smooth out your wrinkles The hormone oestrogen is pumped out during sex, which can in turn have a plumping effect on the skin, helping to smooth out those fine lines. This is especially useful following the menopause, when a woman’s skin can become drier and more wrinkled, as oestrogen levels naturally drop. One American study found that menopausal women who had sex every week had oestrogen levels that were twice as high as their counterparts who abstained. 12 Give yourself an all-over healthy glow According to research carried out at the Royal Edinburgh Hospital, sex promotes skin renewal because it is an aerobic form of exercise. The scientist behind this study found that vigorous sex pumps higher levels of oxygen around the body, increasing the flow of blood and nutrients to the skin, and pushes newer, fresher skin cells to the surface, making skin look healthier. 13 Improve your self-esteem One of the most important benefits, noted in a recent survey undertaken by the University of Texas, US, was that participants who had sex regularly felt more confident about their bodies. 14 Lower your blood pressure A Scottish study found men and women who had plenty of sex coped well with stress and had lower blood pressure than those who abstained. Researchers at Brigham Young University in the US also linked frequent intercourse to lower blood pressure. 15 Banish depression Like any exercise that raises your heart rate, sex causes your brain to release feel-good chemicals that boost your levels of serotonin – the happy hormone – to lift your mood. Serotonin is the body’s key antidepressant chemical and one of the major reasons people smile and feel happy and relaxed after sex. Sexually active women in long-term relationships are also less likely to feel depressed than women who go without sex, according to a study of nearly 300 women by psychologist Gordon Gallup in the American Archives Of Sexual Behavior. 16 Cure that headache (yes, really!) “Having a headache” might be an age-old excuse not to have sex, but the scientific evidence says that, to the contrary, sex can help shift pain! This is because making love causes a surge in the “love” hormone oxytocin, plus other feel-good endorphins, which can ease pain. Women have reported that their pain from both headaches and arthritis improved post-coitus. 17 Slash stress In a study in the Psychology journal, researchers found that people who’d had sex in the last 24 hours coped better with stressful scenarios – such as public speaking – than those who had not. Research has also shown that touching and cuddling during and after sex reduces the body’s levels of cortisol – the hormone that is secreted when you’re stressed. 18Kick your insomnia into touch The oxytocin released when you orgasm has another benefit – it can help you drop off, research claims. Both men and women release this feel-good hormone just before orgasm, and as it courses through your system, it promotes relaxation and sleepiness. So there is actually a genuine excuse for him to fall asleep so quickly after sex... 19 Strengthen your bones As regular sex can boost oestrogen levels in post-menopausal women, it can offer some protection against the bone-thinning condition osteoporosis that is triggered by a lack of oestrogen. And men can benefit too, as testosterone levels have been found to increase during and after sex, which can provide some protection against male osteoporosis. 20 Cut your risk of prostate cancer Researchers at Nottingham University have found that men who enjoy a regular sex life in their 50s are at lower risk of developing prostate cancer. This is because sex clears the prostate of toxins that could otherwise linger and trigger cancerous changes. The link was first suggested after several studies showed that monks appeared to have a higher chance of developing prostate cancer. 21 Feel better all day If you decide to go for a spot of morning passion to start your day, the boost to your mood it provides can continue right through until night-time, according to research. The American scientist Dr Debby Herbenick found that adults who made love first thing in the morning were not only more upbeat for the rest of the day, but they also benefited from a stronger immune system than those people who simply opted for a cup of tea and some toast before heading out of the door. In other words – why wait until tonight? Posted by dewi darmawati at 3:43 AM
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tuesday, july 9, 2013
More Dry Eyes in the House http://online.wsj.com/article/SB10001424127887324867904578594000939418538.html? mod=e2fb by S U M A T H I R E D D Y Dry-eye syndrome is growing, and doctors blame smartphones, office buildings.
An Ocean of Tears: The pharmacy eye-care aisle reveals many types of drops aimed at people suffering from dry eyes. They vary by formula and viscosity. A growing number of people are landing in their doctor's office complaining of gritty, irritated and burning eyes. No, it isn't allergies or an eye infection. Most of these patients are suffering from dry eye, a condition that affects as many as 25 million Americans, according to eye-care industry estimates. Eye doctors say dry-eye syndrome is especially prevalent among women and older people and is the second most common complaint after vision problems. "It's an epidemic now," said Stephanie Marioneaux, an ophthalmologist in Chesapeake, Va. "At one point primarily it was postmenopausal women. Now I have all kinds of dry-eye patients." Behind the growing number of cases: Mucus membranes that produce a key component of tears naturally dry up as people age. Spending a lot of time in lowhumidity environments, such as air-conditioned office buildings or airplane cabins, also can promote dry eye, as a recent study published in the journal Cornea found. And staring at a computer or smartphone screen for long periods also can contribute to dry eye, as people forget to blink. "I have patients who have jobs that require them to stare at a computer all day," said Dr. Marioneaux. "I have them put a sticker on their computer that says, 'Blink!' " Ideally, a person should blink 12 to 15 times a minute, she said. Other reasons behind dry eye can include certain autoimmune diseases, and medications like antihistamines and antidepressants. Some eye surgeries, such as Lasik, can cause temporary dryness. Dry and windy climates can contribute to dry eye, as can contact lens intolerance and eye makeup. There are two main types of dry eye. One occurs when your eyes aren't producing enough tears. For a long time, doctors believed this was the main culprit. But in recent years there has been recognition that poor tear quality, often referred to as evaporative dry eye, is far more prevalent, accounting for the majority cases. Many
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people have both problems. Coating the surface of the eye is a protective tear film that consists of three main components—an outer, oily layer that prevents evaporation and a watery layer mixed with bits of a gel-like substance called mucin that holds the tear film to the eye. Evaporative dry eye occurs when the so-called meibomian glands, located in the upper and lower eye lids, don't produce enough oil, or the oil isn't of high quality. This causes the watery layer of the tears to evaporate more quickly. Every time you blink and your top lid touches the bottom lid, the meibomian glands squirt oil that stabilizes the tear film, said Dr. Marioneaux. "If you're not blinking completely, which actually a lot of people do, you're not getting the release of this oil. So oil backs up in the lid and begins to get thicker and starts to clog up the oil gland," she said. Most dry-eye patients have relatively mild symptoms, which can include a gritty feeling, burning or itching and sometimes blurry vision. Excessive tearing can occur when the body responds to the dryness by producing more tears as a protective mechanism. More severe cases can result in a stabbing pain caused by exposed nerves on the dried surface of the eye that become irritated from the formation of microscopic erosions. Brad Feldman, a cornea, cataract and refractive surgeon at Wills Eye Institute in Philadelphia, said contact-lens wearers with dry eye can be more prone to infection and irritation, such as getting a scratch on the eye. Finding the right treatment to reduce dry-eye symptoms can involve trying different products and approaches. Most people start with over-the-counter drops to replenish moisture and tears. Some of the newer products also try to address evaporative dry eye by replenishing the tear film's oil layer. For patients who use drops more than three or four times a day, doctors recommend getting products without preservatives, which can cause some discomfort. Preservatives are sometimes added to drops to prolong their shelf life while keeping bacteria at bay. Gel drops and ointment can help in cases of severe dry eye. These treatments may cause blurred vision so are usually recommended for nighttime use. They are also recommended if patients have a condition in which the eye doesn't fully close at night when sleeping. Some patients also benefit from the use of an anti-inflammatory such as steroids or omega-3 fatty acids to reduce inflammation of the glands, or antibiotics, taken orally or topically. Allergan's Restasis, an anti-inflammatory eye drop, is the main prescription drug used, primarily for individuals who don't produce enough tears. Dr. Feldman said antibiotics also appear to alter the eye's oil production although it isn't clear exactly how. He said he is currently involved in a study testing the application of an antibiotic to the eyelid margin to see if it can improve the quality of the oil in the tear film. Another procedure to treat dry eye is called punctal plugs. The puncta—the hole in the corner of the eyelid where tears drain to the back of the nose and down the throat —is plugged so tears stay in the eye longer. The hole can also be permanently closed with heat in a more invasive procedure. For evaporative dry eye, experts recommend warm compresses or eye massage to unclog the glands. Kristin Hammersmith, a corneal surgeon at Wills Eye Institute in Philadelphia said she tells patients to use compresses two times a day for five minutes each time. Dr. Hammersmith said she has begun using a new treatment for evaporative dry eye patients, called LipiFlow. The device, made by TearScience, a Morrisville, N.C., company, is designed to unclog the meibomian glands in a 12-minute procedure that involves clamping and squeezing the eyelids while heating them to remove blockage from the glands. A company-funded study published in the journal Cornea last year, involving 139 dry-eye patients, found the treatment worked significantly better than applying hot compresses. Dr. Hammersmith said it isn't clear how long the LipiFlow treatment lasts but she believes it is effective for six to 12 months based on her patients' experiences. The company claims the procedure lasts between nine and 15 months. The treatment costs about $850 per eye and isn't covered by insurance, Dr. Hammersmith said. Sometimes dry eye can be brought on by other conditions. Anne Slattery, a patient at Wills Eye Institute, has suffered from dry eyes since 2008, when she was also diagnosed with corneal disease and ocular rosacea, an inflammatory condition. The 60-year-old said she believes another cause of the dry eye was her age, as she was going through menopause at the time. Ms. Slattery, who continues to be treated for her eye disorders, also has sought to alleviate symptoms of dry eye. Her doctors initially recommended hot compresses four times a day, eye drops every hour and an antibiotic ointment at night. She stopped wearing makeup. Staring at a computer made it worse. "I eventually quit my [administrative-assistant] job because I couldn't do it anymore." She got a punctal plug in both eyes in 2009, which helped some. Last year she got the LipiFlow treatment and she said she has been happy with the results. "I didn't notice the change right away," said Ms. Slattery, of Bristol, Pa. "I still do the compresses and use the tear drops every three to four hours and the antibiotic cream. It's maintenance." Posted by dewi darmawati at 3:50 PM
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friday, july 5, 2013
Hypertriglyceridemia: its etiology, effects and treatment http://www.cmaj.ca/content/176/8/1113.full
George Yuan, Khalid Z. Al-Shali, Robert A. Hegele From the Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont.
Hypertriglyceridemia refers to a fasting plasma triglyceride measurement that is increased, typically above the 95th percentile for age and sex — although additional quantitative or qualitative lipoprotein abnormalities can ,
also be present. 1 2 Patients can fluctuate between hypertriglyceridemic states: given an appropriate metabolic stress, mild or moderate hypertriglyceridemia can deteriorate into severe hypertriglyceridemia. Elevated plasma triglyceride concentrations contribute to increased risk of cardiovascular disease, both directly and because such elevations “keep bad company” with associated risk factors such as obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes mellitus. 2 The increased risk of acute pancreatitis is an additional consideration when a patient's triglyceride level is very high (typically > 10 mmol/L). The two main sources of plasma triglycerides (also known as triacylglycerol) are exogenous (i.e., from dietary fat) and carried in chylomicrons, and endogenous (from the liver) and carried in very-lowdensity lipoprotein (VLDL) particles. In capillaries within fat and muscle tissue, these lipoproteins and chylomicrons are hydrolyzed by lipoprotein lipase into free fatty acids. After a meal, over 90% of the circulating triglycerides originate in the intestine and are secreted in chylomicrons, whereas during periods of fasting, endogenous triglycerides secreted by the liver as VLDL predominate. The increase in plasma of triglyceride-rich lipoproteins results from increased production from the liver and intestine (by means of upregulated synthetic and secretory pathways) or through decreased peripheral catabolism (mainly from reduced lipoprotein lipase activity).
Classification Hypertriglyceridemia can be divided into primary and secondary types. In this postgenome era, a classification system for triglyceride disorders should be based upon molecular diagnoses, but a molecular basis for primary hypertriglyceridemia has been found in less than 5% of cases — and for secondary cases, no genetic susceptibility component that is reproducible. 1Most patients with hypertriglyceridemia have at least one secondary factor; nevertheless, not everyone with equivalent exposure to secondary factors develops equally severe dyslipidemia, which suggests a role for endogenous primary monogenic or polygenic susceptibility. The Adult Treatment Panel III 3 of the National Cholesterol Education Program has suggested 4 triglyceride strata in the context of assessment of risk of cardiovascular disease: normal (< 1.7 mmol/L), borderline high (1.7–2.3 mmol/L), high (2.3–5.6 mmol/L) and very high (> 5.6 mmol/L). An alternative scheme, the World Health Organization–supported Fredrickson system of hyperlipoproteinemia phenotypes, was at one time widely taught, but has fallen into disuse. Here we review hypertriglyceridemia using clinical descriptive names, with corresponding Fredrickson numerical types included (in parentheses) for crossreference with older literature. Primary hypertriglyceridemia Chylomicrons normally are cleared rapidly from plasma by lipoprotein lipase with apolipoprotein (apo) C-II as a cofactor. Familial chylomicronemia (hyperlipoproteinemia type 1, in the Fredrickson system) and primary mixed hyperlipidemia (type 5) are each characterized by the pathologic presence of chylomicrons after a 12–14-hour period of fasting. Clinical features observed in both familial chylomicronemia and primary mixed hyperlipidemia include eruptive xanthomata (Fig. 1A), lipemia retinalis (Fig. 1C), hepatosplenomegaly, focal neurologic symptoms such as irritability, and recurrent epigastric pain with increased risk of pancreatitis. Samples of lipemic plasma develop a creamy supernatant when refrigerated overnight (Fig. 1B); when the plasma is tested, fasting triglyceride measurements are typically above 10 mmol/L in cases of either familial chylomicronemia or primary mixed hyperlipidemia.
Fig. 1: Clinical manifestations of primary hypertriglyceridemia. A:Eruptive cutaneous xanthomas (here on a patient's knee) are filled with foam cells that appear as yellow morbiliform eruptions 2–5 mm in diameter, often with erythematous areolae. Most often associated with markedly elevated plasma chylomicrons in cases of familial chylomicronemia (hyperlipoproteinemia type 1) or primary mixed dyslipidemia (hyperlipoproteinemia type 5), they usually occur in clusters on the skin of the trunk, buttocks or extremities. B: Lipemic plasma. Whole blood has been allowed to stand at 4°C overnight. The sample on the left comes from a patient whose fasting total cholesterol result was 14.2 mmol/L and triglyceride concentration was 41.8 mmol/L. The sample on the right comes from a normolipidemic subject. C: Lipemia retinalis. A milky appearance of the retinal vessels and pink retina can be seen when plasma triglyceride concentration exceeds 35 mmol/L. D: Tuberous xanthomas, filled with foam cells, appear as reddish or orange, often shiny nodules, up to 3 cm in diameter. They are usually moveable and nontender. In patients with familial dysbetalipoproteinemia (hyperlipoproteinemia type 3), they usually appear on extensor surfaces; these are on a patient's elbows. E:Palmar crease xanthomas are filled with foam cells and appear as yellowish deposits within palmar creases. These skin lesions are pathognomonic for familial dysbetalipoproteinemia (hyperlipoproteinemia type 3). Photo by: Panels A, B and D are courtesy of Robert A. Hegele; panel C is courtesy of Ted M. Montgomery; and panel E is courtesy of Jean Davignon. Key distinguishing features of familial chylomicronemia and primary mixed hyperlipidemia include initial manifestation during childhood for the former and in adulthood for the latter; biochemically proven deficiency of lipoprotein lipase, apo CII activity or homozygous gene mutations in the former, with less severe functional deficiency and infrequent detection of gene mutations in the latter; a much lower population prevalence of the 6 3 former (about 1:10 ) than of the latter (about 1:10 ); frequent presence of secondary factors in the latter; and a greater elevation of total cholesterol in the latter, relative to that in familial chylomicronemia. In biochemical diagnosis, familial chylomicronemia features a loss of lipoprotein lipase activity in plasma collected after an intravenous dose of heparin; however, few laboratories still perform this test. Familial hypertriglyceridemia (hyperlipoproteinemia type 4) is defined by an isolated elevation of VLDL, which is not as triglyceride-rich as chylomicrons are. This familial disorder has a population prevalence of some 5%–10%. Its molecular basis is still largely unknown but is likely to be polygenic, requiring a secondary factor for expression. 1 Typically, patients with this disorder have moderately elevated plasma measurements of triglycerides (3–10 mmol/L), often with low levels of high-density lipoprotein–cholesterol (HDL-C). Familial hypertriglyceridemia is associated with increased risk of cardiovascular disease, obesity, insulin resistance, diabetes, hypertension and hyperuricemia. The inheritance pattern of familial combined hyperlipoproteinemia (type 2B) is one of an autosomal dominant with variable penetrance, with a population prevalence of 2%–5%. 4 The defining lipoprotein abnormalities are increased VLDL and low-density lipoprotein (LDL) with depressed HDL, associated with an abnormal lipoprotein profile in at least one first-degree relative. Affected people occasionally have obligate heterozygosity for LPL or APOC3 gene mutations, but the molecular basis underlying familial combined hyperlipoproteinemia is unknown in most instances. 1 A recently defined gene that may be causative for this disorder is USF1, which encodes an upstream stimulatory factor, 5 although several other genes (including APOA5 andAPOC3) have been variably claimed as causative. 6 Finally, familial dysbetalipoproteinemia (hyperlipoproteinemia type 3) has a population prevalence of 1–2 in 20 000. 7 The main observable lipoprotein abnormality is an increase in triglyceride-rich lipoprotein remnants, also known as intermediate-density lipoproteins or -VLDL, which produce an equimolar elevation of plasma total cholesterol and triglyceride measurements. 7 People with this disorder typically are homozygotic for the binding-defective APOE E2 isoform, which differs from the common E3 isoform by a substitution of cysteine for the normal arginine at residue 158 in the receptor-binding domain. Phenotypic expression, however, usually requires accompanying factors such as obesity, type 2 diabetes or hypothyroidism. 7 Plasma levels of LDL are decreased because of interrupted processing of VLDL. An increased VLDL-C: triglyceride ratio and E2/E2 homozygosity are diagnostic. Affected people often have tuberous or tuberoeruptive xanthomata on the extensor surfaces of their extremities (Fig. 1D), planar-or palmar-crease xanthomata (Fig. 1E) and increased risk of cardiovascular disease. Secondary hypertriglyceridemia Some metabolic conditions are frequently (but not universally) associated with high triglyceride results, suggesting that people who develop secondary hypertriglyceridemia might have a subtle inherited metabolic defect that confers susceptibility. Obesity is probably the metabolic stressor most frequently associated with hypertriglyceridemia, although associations with poorly controlled type 2 diabetes and excessive alcohol consumption are also common. Obesity, metabolic syndrome, diabetes. People with excess visceral adipose tissue often have elevated triglyceride and low HDL-C levels. About 80% of men with a waist girth of 90 cm or more and a plasma triglyceride level of 2 mmol/L or more typically have a metabolic triad of nontraditional cardiovascular-disease markers: hyperinsulinemia and increased levels of apo B and small, dense LDL particles. This triad can increase the risk of cardiovascular disease by up to 20 times. 8 Impairment of the ability of insulin to stimulate glucose uptake and inadequate compensation for insulin insensitivity underlie type 2 diabetes. Moreover, among insulin-resistant people without type 2 diabetes, hyperinsulinemia is associated with a cluster of metabolic abnormalities called the metabolic syndrome. 9 This syndrome, seen in people with central obesity, strongly predicts a future onset of type 2 diabetes. It is characterized by glucose intolerance, dyslipidemia (specifically, triglycerides > 1.7 mmol/L and low HDL-C concentrations) and hypertension. 3 Hypertriglyceridemia, both in the metabolic syndrome and in type 2 diabetes, results from increased plasma concentrations of VLDL, with or without chylomicronemia; 9 deficient lipoprotein lipase activity; increased cholesteryl ester transfer protein activity; and increased flux of free fatty acids to the liver. A fatty liver is often associated with hypertriglyceridemia in people with obesity and insulin resistance. Several definitions of the metabolic syndrome exist, 9 and it has been debated whether the clustered risk factors impart any risk above the simple sum of the individual components. However, the concept of the metabolic syndrome has proven to be useful in emphasizing the importance of obesity, insulin resistance and related lipoprotein disturbances in the assessment of cardiovascular disease risk. Hypertriglyceridemia of obesity, the metabolic syndrome and type 2 diabetes improves with weight loss and glycemic control. Alcohol. Hypertriglyceridemia associated with alcohol intake also mainly results from increased plasma VLDL, with or without chylomicronemia. In some alcohol users, plasma triglyceride measurements can remain within the normal range because of an adaptive increase in lipolytic activity. However, alcohol can also impair lipolysis, especially when a patient has a pre-existing functional deficiency of lipoprotein lipase, which leads to markedly increased plasma triglycerides. Renal disease. Although elevated LDL-C is the dominant abnormality, nephrotic syndrome is also characterized by increases in apo B– containing lipoproteins, including VLDL. The complex relation between renal disease and lipoprotein metabolism is reviewed in depth elsewhere, 10 but the underlying mechanisms probably include overproduction by the liver, which concurrently increases albumin synthesis to compensate for renal protein wasting. Uremia is associated with elevated VLDL, which reflects impaired lipolysis, possibly from the toxic effect of uremic metabolites. Pregnancy. During the third trimester of pregnancy, plasma triglyceride levels normally rise to as much as threefold, 11 but this physiologic triglyceride increase has little clinical consequence. Marked triglyceride increases also result, however, when lipoprotein lipase activity is compromised. Although chylomicronemia during pregnancy is very rare, it can be complicated by pancreatitis, which can be fatal to both mother and fetus. 12 Nonalcoholic fatty-liver disorder. This disorder may affect up to one-third of North Americans, which reflects the increasing prevalence of obesity, ,
insulin resistance and metabolic syndrome. 13 14 Among affected patients, up to one-third may also have nonalcoholic steatotic ,
hepatitis. 13 14 Lipotoxicity, oxidative stress, cytokines and proinflammatory mediators contribute to the progression from steatosis to nonalcoholic steatotic hepatitis. Elevated triglyceride and depressed HDLC levels are the defining components of the dyslipidemia in nonalcoholic fatty-liver disorder. Small studies have indicated that treatment with statins is more effective than that with fibrates in correcting the dyslipidemia. 15 Other medical conditions. Although hypothyroidism is usually associated with elevated LDL concentrations, triglycerides may also be elevated. Paraproteinemias (e.g., hypergammaglobulinemia in macroglobulinemia, myeloma, lymphoma and lymphocytic leukemias) and autoimmune disorders (e.g., systemic lupus erythematosis) can also cause hypertriglyceridemia, probably through immune-mediated interference of lipolysis. Medications. Many drugs increase triglyceride concentrations (Box 1). If one is considered to cause hypertriglyceridemia, the indications for that medication should be reviewed. If dosage reductions, changes in route of administration or substitution with another class of medication are not practical, then marked elevations of triglycerides should be treated with diet or pharmacologic agents.
Patients taking highly active antiretroviral therapy, particularly protease inhibitors, frequently experience lipodystrophy, insulin resistance and dyslipidemia; up to 80% and 50% of patients develop hypertriglyceridemia and hypercholesterolemia, respectively. 16 Combination highly active antiretroviral therapy was found to be associated with a 26% increase in relative risk of cardiovascular disease. 17 Ritonavir and lopinavir are most strongly associated with dyslipidemias; 16 3 reverse-transcriptase inhibitors, the nucleoside stavudine and the nonnucleoside nevirapine16 and efavirenz, 18 less consistently so. Often, triglyceride levels can improve when agents are switched (if there is no compromise ,
in antiretroviral efficacy). 18 19 In one study, 19 for instance, a change from a protease inhibitor to nevirapine or efavirenz reduced triglyceride levels by about 25%; the addition of pravastatin or bezafibrate further reduced them by about 40%. Second-generation antipsychotic medications are known to be associated with obesity, hypertriglyceridemia, 20 hyperglycemia and type 2 diabetes. 21Clozapine and olanzapine disturb metabolism the most; risperidone and quetiapine have intermediate effects; and aripiprazole and ziprasidone, the fewest. 20 Psychiatric disorders, because of associated lifestyles, may also predispose those affected to metabolic disturbances. 22 Patients taking second-generation antipsychotics should be monitored regularly (every 8–12 months) for weight gain and changes in fasting plasma glucose and lipoprotein levels. 21
Triglycerides and atherosclerosis Moderate hypertriglyceridemia is almost certainly an independent risk factor for cardiovascular disease. The Prospective Cardiovascular Munster (PROCAM) study 23 found increases in risk as triglyceride levels rose from 2.3 mmol/L to 9.0 mmol/L (after correction for other risk factors for cardiovascular disease). Other studies 24 have shown a strong independent relation between plasma triglyceride levels and likelihood of cardiovascular disease. Meta-analyses of thousands of patients followed up for more than 10 years showed that a triglyceride elevation of 1 mmol/L increased risk of cardiovascular disease by 32% in men and 76% in women, independent of HDL-C levels. 25 Complex mechanisms that underlie the association of triglycerides and atherosclerosis obscure the detection of any direct causal relation. Proatherogenic metabolic or biochemical abnormalities (e.g., obesity, type 2 diabetes, decreased levels of HDL-C, increased small dense LDL, increased free fatty acids, dysglycemia, hyperinsulinemia, increased plasma viscosity, increased inflammatory molecules, impaired fibrinolysis, prothrombosis) are often associated with elevated levels of ,
,
triglycerides. 2 24 25 Furthermore, triglyceride-rich lipoproteins and their remnants may directly contribute to the formation of arterial-wall foam cells. Chylomicrons are not directly atherogenic, although there are rare reports of atherosclerosis in patients with hyperchylomicronemia. 26 In contrast, chylomicron remnants, VLDL and intermediate-density liproproteins are atherogenic. 27 A newer concept is that postprandial lipemia is an independent predictor of cardiovascular disease, 28although, since sample preparation and assay conditions are nonroutine, “postprandial” elevation of triglycerides has no operative definition.
Hypertriglyceridemia and pancreatitis Hypertriglyceridemia increases the risk of acute pancreatitis, accounting –
for a minor but clinically relevant proportion of cases. 29 32 Although a few patients can develop pancreatitis when their fasting triglyceride concentration is 5–10 mmol/L, its risk becomes clinically significant when fasting measurements exceed 10 mmol/L, a level at which chylomicrons –
are present. 29 32 A threshold value of 1000 mg/dL (about 11.3 mmol/L) is often cited, but the clinical relevance and implications of a rounded threshold of 10 mmol/L for “very high” triglycerides are comparable. The capacity of the pancreas to produce an exocrine lipase might explain the specificity of pancreatic involvement. Some patients with triglyceride-related pancreatitis probably have preexisting abnormalities in their metabolism of lipoprotein. 1 Pancreatitis risk is accentuated by any factor that can increase plasma triglycerides past 10 mmol/L. Triglyceride-induced pancreatitis can be preceded by episodic nausea and epigastric pain, during which serum amylase may not exceed common diagnostic cutoffs. Associated clinical clues include eruptive xanthomata or lipemia retinalis (Fig. 1). The onset of full-blown acute pancreatitis can be prevented by restriction of dietary fat or the use of fibrates. Treatment of acute cases includes hemodynamic stabilization, cessation of all oral intake, placement of a nasogastric tube and control of metabolic disturbances. Restricted energy intake is associated with a brisk decrease in plasma triglyceride levels. Plasmapheresis has been attempted in extreme cases, but the benefit was transient. The threshold for developing pancreatitis can vary widely; some asymptomatic people live with triglyceride levels chronically in excess of 40 mmol/L.
Nonpharmacologic treatment People with hypertriglyceridemia are frequently obese, insulin-resistant, hypertensive or diabetic, all of which are risk factors for cardiovascular disease. Treatment includes weight reduction, dietary modification and exercise. Dietary modification should decrease weight, overall energy intake, and intakes of fat and refined carbohydrates (i.e., foods with a high glycemic index). 33 Alcohol consumption should be reduced or eliminated. In cases of severe hyperchylomicronemia, recommended fat intake is restricted to 10%–15% of total energy intake (about 15–20 g/d), with reductions in saturated, unsaturated and trans fats. 3 Consultation with a dietician can be very helpful. For less severe cases of hypertriglyceridemia, restrictions to saturated and trans fat intake and increased aerobic activity can reduce plasma levels of triglycerides. The National Cholesterol Education Program advises a carbohydrate intake of 55%–60% and a protein intake of 15%–20% of daily dietary intake, whereas total and saturated fat should not surpass 30% and 7%, respectively. 3 Plasma triglyceride response to diet and weight loss is about 25%, 34 with marked variation among patients. 34 Omega-3 fatty acids (e.g., eicosapentaenoic and docosahexaenoic acid) are components of both the Mediterranean diet and of fish oils. 35 Daily consumption of 4 g of omega-3 fatty acids, along with with restricted energy and saturated-fat intakes, can reduce plasma triglyceride levels by as much as 20%. However, omega-3 fatty acids are rarely effective when used as the sole triglyceride-lowering therapy.
Pharmacologic therapy to lower the risk of cardiovascular disease In general, monotherapy with a pharmacologic agent should be attempted first, together with dietary adjustments. Combination treatment may be required for refractory severe hypertriglyceridemia, but should be attempted only with caution and frequent monitoring of serum concentrations of creatine kinase, transaminase and creatinine. Fibrates Fibric acid derivatives such as gemfibrozil, bezafibrate and fenofibrate are a mainstay of hypertriglyceridemia treatment. 36 These fibrates can reduce plasma triglyceride levels by up to 50% and raise plasma HDL-C concentrations as much as 20% (although these percentages vary). The complex mechanism of action of fibrates includes modulation of the activity of peroxisome proliferator–activated receptor- in the liver, with reduced hepatic secretion of VLDL and increased lipolysis of plasma triglycerides. 37Fibrates reduce the quantity of small, dense LDL particles and increase HDL-C. 38 Fibrates can sometimes raise plasma LDL-C concentration, which in turn necessitates a change to another drug or the addition of a second agent. Fibrate therapy is generally very well tolerated, with very rare reports of it leading to hepatitis or myositis. 36 The effectiveness of fibrates in reducing cardiovascular disease –
outcomes has been of long-standing concern. Earlier studies 38 40 showed that fibrates reduced cardiovascular event rates; for instance, gemfibrozil resulted in a statistically significant benefit among men with high triglyceride and low HDL-C readings. 40 The recent Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study found that plasma triglyceride, LDL and HDL-C levels in diabetic patients responded favourably to treatment with fenofibrate, but the reduction in the prespecified end point of cardiovascular disease (16%) was nonsignificant. 41 Secondary and tertiary outcomes (e.g., nonfatal myocardial infarction, coronary revascularization, and progression of albuminuria and retinopathy) were significantly reduced. Serum creatinine was about 15% higher in the group taking fenofibrate and fell when fenofibrate was discontinued, which suggests a functional rather than a structural change. 41However, subgroup analyses showed significant benefits of fenofibrate in patients without prior cardiovascular disease and after adjustment for “drop-in” statin use in the placebo group (i.e., increased use of prescribed statins by patients not treated with fenofibrate). Thus, enthusiasm for fibrate therapy is lower than that for statins, although selected patients might benefit. 42 Statins Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. Newer statins used at higher doses can markedly reduce levels of triglycerides. They are not, however, a first-line therapy when triglyceride levels exceed 5 mmol/L. An advantage of statins is the preponderance of evidence for reductions in coronary heart disease end points, 43 especially among patients with type 2 diabetes. 44 Like fibrates, statins are generally well tolerated and rarely cause myopathy or hepatic toxicity. Safety data from the FIELD study showed no rhabdomyolysis among the more than 1000 patients who took both fenofibrate and a statin. 41 Potential beneficial effects of the combination of a statin and fibrate in the treatment of type 2 diabetes are currently being investigated in the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. 45 Niacin The daily consumption of up to 3 g of niacin (nicotinic acid) can lower plasma triglyceride levels by up to 45%, raise plasma HDL-C by up to 25%, and reduce plasma LDL-C by up to 20%. 46 Older clinical trials suggested a reduction in cardiovascular events related to niacin treatment. 47 However, niacin frequently causes light-headedness, cutaneous flushing, or pruritus. These adverse effects can be minimized by starting therapy at low doses then gradually increasing the daily dose; concomitant use of acetylsalicylic acid; or use of longer-acting preparations, such as Niaspan. 48 Less common adverse effects include elevations of liver enzymes, increased levels of uric acid, gastrointestinal distress and worsened glucose tolerance. Other lipid-lowering medications Bile acid–binding resins worsen plasma triglyceride concentrations, 36 whereas cholesterol-absorption inhibitors (e.g., ezetimibe) do not. 49 A combination of fenofibrate and ezetimibe was recently shown to be safe and effective for patients with elevated triglyceride and LDL-C levels. 50 Canada recently joined the United States in approving this combination for therapeutic use. Emerging treatments Rimonabant is a cannabinoid-1 receptor antagonist that decreases hunger ,
and reduces food intake. 51 52 Four phase-3 randomized, double-blind, placebo-controlled trials (the Rimonabant in Obesity trials, namely RIO– –
Europe, –Lipids, –North America and –Diabetes)52 56 have each evaluated rimonabant in various patient groups, showing successful, persistent reductions in obesity variables in the treatment groups, with concomitant improvements in metabolic biomarkers, including – triglycerides. 52 56 However, adverse effects such as depression and
anxiety were also more common in those groups. 54Nonetheless, rimonabant seems to be a promising new treatment for obesity and dyslipidemia. Glitazar drugs are dual agonists of peroxisome proliferator-activated receptor- (similar to fibrates) and - (similar to thiazolidinediones) and hold theoretical advantages for treatment of type 2 diabetes and metabolic syndrome. However, an analysis of phase 2 and 3 trials found significant associations between muraglitazar and death, myocardial infarction and stroke. 56 This agent and others of the class have since been withdrawn from clinical use. LPL gene therapy. Hyperlipoproteinemia type 1 caused by lipoprotein lipase deficiency causes recurrent and potentially fatal pancreatitis. 1 The incidence of lipoprotein lipase deficiency can be up to about 1:5000 in regions of Eastern Quebec because of a genetic founder effect; 57 in such populations, gene therapy is an interesting, if still theoretical, consideration. Management of lipoprotein lipase deficiency with fibrates is modestly effective. As for nonpharmaceutical treatments, most patients find it difficult to adhere to the recommended diet of less than 10% (of total energy intake from) fat. Even with aggressive management, plasma triglyceride levels in patients with familial chylomicronemia often remained over the 10 mmol/L threshold. Gene therapy, however, may help treat monogenic lipoprotein lipase deficiency, 58 since lipoprotein lipase can be targeted to skeletal muscle: a modest increase in activity would then dramatically reduce plasma triglyceride levels. Using a “beneficial” allele of LPL, gene therapy has corrected elevated triglyceride levels in animals, 59 which paves the way for trials involving people.
Target triglyceride goals In 2006, guidelines from the Canadian Working Group on Hypercholesterolemia and Other Dyslipidemias no longer recommended a specific triglyceride target, 60 whereas those from the National Cholesterol Education Program in the United States recommended that if triglyceride concentration exceeds 1.7 mmol/L, therapy should be aimed at attaining the LDL-C target specified for the patient's risk stratum of coronary heart disease. 3 Table 1 presents a proposed strategy for management of patients whose triglyceride levels are elevated.
Conclusions Moderate hypertriglyceridemia is a risk factor for cardiovascular disease; severe hypertriglyceridemia, for pancreatitis. Although reductions in plasma triglycerides probably reduce the risk of cardiovascular disease, the clinical trial evidence for fibrate monotherapy is weaker than that provided for reductions of plasma LDL-C concentrations. Nonetheless, improvement of triglyceride levels by control of secondary factors will help reduce risk of cardiovascular disease. The use of fibrates as prophylaxis against pancreatitis when plasma triglyceride results exceed 10 mmol/L is less contentious. In the next few years, new clinical trials (especially of statin–fibrate combination treatment) and the availability of new types of treatment may result in an evolution of the current approach to treating elevated plasma triglycerides.
Footnotes This article has been peer reviewed. Contributors: Khalid Al-Shali and Robert Hegele drafted the manuscript. George Yuan and Robert Hegele participated in the critical revision of the article. All authors have approved the final version for publication. Acknowledgements: We were supported by the Jacob J. Wolfe Chair in Functional Genomics, the Edith Schulich Vinet Canada Research Chair (Tier I) in Human Genetics, a Career Investigator award from the Heart and Stroke Foundation of Ontario and operating grants from the Canadian Institutes for Health Research, the Heart and Stroke Foundation of Ontario, the Ontario Research Fund, and Genome Canada through the Ontario Genomics Institute. George Yuan was supported by the University of Western Ontario Summer Research Training Program and by the Heart and Stroke Foundation of Ontario's Irwin Bernick Scholarship. Competing interests: None declared.
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