Basel, Switzerland - The results of a large review analyzing the effects of different lipid-lowering medications and dietary interventions reinforces the benefit of statin therapy to significantly reduce the risk of overall and cardiac mortality. The report also highlights the cardiovascular and overall benefits of omega-3 (n-3) polyunsaturated fatty acids, finding that the beneficial component of fish and/or fish-oil supplements also reduces the risk of death.
"Our study confirms the benefit of statins in reducing the risk of overall and cardiac mortality in patients with or without CHD and additionally shows that n-3 fatty acids reduce overall and cardiac mortality in patients with CHD," write Dr Marco Studer (University Hospital Basel, Switzerland) and colleagues in the April 11, 2005 issue of the Archives of Internal Medicine. "In contrast, we found no reduction in overall mortality and an increased risk of death from noncardiovascular causes in individuals taking fibrates compared with individuals in placebo or control groups."
Our study confirms the benefit of statins in reducing the risk of overall and cardiac mortality in patients with or without CHD.
To analyze the existing data as part of their meta-analysis, the investigators included all studies that compared any lipid-lowering intervention with placebo or usual care, had follow-up of at least six months, and reported mortality data. A total of 97 randomized studies, comprising six lipid-lowering interventions (statins, fibrates, resins, niacin, n-3 fatty acids, and dietary changes), met the eligibility criteria. These studies included 137 140 individuals in the intervention arms and 138 976 individuals in the control arms.
Across these primary- and secondary-prevention studies, investigators found that the risk ratios for overall mortality were significantly reduced with statins and omega-3 fatty acids. For the statins, this effect was consistent in trials of primary and secondary prevention of CHD, but there was not enough evidence to support the beneficial effect of n-3 fatty acids in primary prevention.
Effects of different lipid-lowering interventions on overall mortality
Type of intervention
| Trials (n)*
| Mean follow-up (y)
| Mean cholesterol reduction (%)
| Overall mortality risk ratio (95% CI)
| Heterogeneity, p
|
Statins
| 35
| 2.9
| 20 (7 to 36)
| 0.87 (0.81-0.94)
| 0.05
|
Fibrates
| 17
| 4.4
| 8 (0 to 14)
| 1.00 (0.91-1.11)
| 0.01
|
Resins
| 8
| 3.2
| 15 (8 to 24)
| 0.84 (0.66-1.08)
| 0.86
|
Niacin
| 2
| 4.7
| 11 (8 to 14)
| 0.96 (0.86-1.08)
| 0.81
|
Omega-3 fatty acids
| 14
| 1.9
| 2 (-9 to 4)
| 0.77 (0.63-0.94)
| 0.01
|
Diet
| 17
| 4.2
| 10 (1 to 24)
| 0.97 (0.91-1.04)
| 0.19
|
*In four studies, there were multiple treatment arms. The investigators used the control group for the comparison against all the treatment arms.
The risk of cardiac mortality was also significantly reduced with statins, resins, and omega-3 fatty acids, with the lipid-lowering agents decreasing cardiac mortality by 22%, 30%, and 32%, respectively. Risk ratios for death from other causes showed no association when compared with control groups, with the exception of fibrates (risk ratio 1.13; 95% CI 1.101-1.27). The authors point out that a limited number of trials provided detailed noncardiovascular, cause-specific mortality data, precluding a detailed analysis.
In the discussion section of the paper, Studer et al write that niacin and fibrates have excellent properties to increase HDL cholesterol levels and to reduce triglyceride levels and that current guidelines recommend the use of either drug in patients with hypertriglyceridemia, increased LDL-cholesterol levels, and metabolic syndrome. They point out that if used in appropriate doses, n-3 fatty acids are as effective as fibrates in reducing triglyceride levels but are associated with a reduction in overall mortality. As n-3 fatty acids lower total cholesterol by only very small amounts, the beneficial effects are likely mediated by other means, they add.
Source
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Studer M, Briel M, Leimenstoll B, et al. Effect of different antilipidemic agents and diets on mortality. Arch Intern Med 2005; 165:725-730.
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April 18, 2005 11:28 (EDT)
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Reluctance of doctors to prescribe fish oil
I still find that doctors are very reluctant to prescribe fish oil to their heart patient.
Previous GISSI-P, NHS and Physician Health study were not able to stir the interest.
Hence this latest meta-analysis should be interesting as it showed that fish oils could be even better than statins in the secondary prevention of heart events.
With such overwhelming evidence, it is yet to be seen whether this will translate to more fish oil prescriptions.
Are we talking the same language - we need to help save lives - not to please drug companies. Here is the real test of a doctors' intergrity.
js bhullar |
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April 19, 2005 04:16 (EDT)
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Practical fish oil information
Jagdev,
I appreciate your post on this topic.
Compliance is an issue with fish oil capsules for a variety of reasons.
Since I have personally failed every statin on the market from muscle aches and stomach upset, I was desparate to do something besides my daily exercise routine. I could not easily swallow those foot long fish oil capsules, so I found a liquid supplement that is lemon flavored, tastes great, adds easily to cereal, shakes and salads. No fishy odor either.
It is called "The very finest fish oil" sold by Carlson Laboratories and bottled in Norway. I order it by mail and a 500 cc bottle lasts me about 100 days, costs about 34.00 US dollars per bottle, or if I order several, 27.00 dollars each. The phone number to order is 1-888-234-5656 or wwwcarlsonlab.com.
Each teaspoon provides 1600 mg of Omega-3 Fatty acids, 4 grams of fat and 40 calories. It makes anything you put it in taste better and will prevent you from the hunger of a carb based meal as it provides a little fat.
I do NOT receive any monetary or non-monetary benefit from this company, do not have stock in it and am not associated with it in anyway. I just use their product and think it might be helpful to my patients, and hopefully helpful to yours.
Good luck
Melissa |
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April 20, 2005 08:00 (EDT)
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Suggestion
Consider asking your patients to freeze the fish oil capsules before swallowing them. That seems to help some avoid the GI intolerance
Hisham |
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April 24, 2005 01:11 (EDT)
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Statins useless in women for primary prevention
Melissa,
As a women, presumably with no previous CAD event, why would you even think about taking a statin?
See this paper from JAMA.
Drug Treatment of Hyperlipidemia in Women
Conclusions For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.
JAMA. 2004;291:2243-2252 |
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April 24, 2005 08:13 (EDT)
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PRO-ACTIVITY and EXTRAPOLATION
Ah, Colin,
I guess the most simple explanation is that none of my father's family "had coronary disease" on a Tuesday before they had an MI on Wednesday. Since they start with CAD in their late thirties, and I'm 44, it's a personal choice that I started to try all the statins.(By the way, Baycol 0.2 was the magic trick for me, but alas). I'm all for an event-free life, even if it's not longer. (Isn't that a fair interpretation of the JAMA data?)
With my unmedicated LDL of 199, I go screaming into the night hoping for anything to get my LDL below 90. With tons of exercise, the best I can every do ia 130 off meds. Since there are so many subsets of hyperlipidemia , I figure that individualized care is appropriate for some patients.
I have a seventeen year old on lipitor since her cholesterol is between 350 and 400 when not medicated and her LDL is greater than 250. I know, we should have waited for her first bypass, but her mom just would not hear of it!
I had hoped you would be proud of me for taking fish oil!!! Not that my lipid profile will look any better, but it might get me to fifty!! That and a few stomach crunches and a bike.
Did you not think that recent retro analysis posted looked very good for fish oil? Do you use fish oil?
Melissa
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April 25, 2005 09:25 (EDT)
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Vegan diet
Melissa - is you daughter a vegan?
If not, you may want to read the book called "The China Story". It is written by a academic nutrionist who has done research for 40 years on the relationship between a plant-based diet and diseases like CAD. He believes that animal protein, and not necessarily animal fat, is the causal agent of CAD to the degree that it is related to an animal-based diet. He is an advocate of a whole foods plant-based diet. He also doesn't believe in the need for nutritional supplements (eg. fish oil).
Even if you are not convinced by his thesis, it is a fascinating book. I have decided to become a vagan for one year to see what effect it has on my weight and health.
Jeff.
Jeff. |
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April 25, 2005 02:02 (EDT)
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Sounds in intriguing
Jeffrey,
thanks so much for the information, but I did want to clairfy that the 17 year old is not my daughter, but a patient.
I'd be interested in knowing how your Vegan diet comes out over the next year. I'm a carnivore (didn't suprise you did it?!!!HA, but I only eat ultra low fat red meat less than weekly. I eat tons of grilled fish and chicken though!)
I appreciate your input!
May your VAP become perfect!!!!
Melissa |
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April 25, 2005 02:48 (EDT)
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Melissa, what is VAP?
I no longer eat red meat (or at least have dramatically cut down on my red meat consumption). This is not just due to cholesterol issues, but here, north of the border, we have had several cases of mad-cow diseases (bovine spongiform encephalopathy) in Canadian cows. A recent documentary by David Suzuki confirmed that our industrial controls on rendered meat (ie, meat unnaturally fed to animals before they die) is still far too lax. Frighteningly, this also applies to chickens and pigs, who are allowed to consume rendered meat of the same species before they are slaughtered (does anyone remember kuru?). |
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April 25, 2005 06:09 (EDT)
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This Esoterica may occaionally come in handy.
Dan, at the risk of snickers by any bonefide lipidologist, which I'm not, I'll take a stab at this.I've just been reviewing this information today as I'm trying to get a handle on it . My tendency is to look at this monster of a report whenver I order one, declare myself illiterate and just try to get the LDL down a little further! So here goes:
The VAP test relies on ultracetrifugation of LDL for direct measurement instead of the Friedewald equation which is inaccurate in face of elevated TG's and low LDL's less than 100. It also measures HDL-C, VLDL-C, Lp(a)-C, R-LDL, IDL-C, LDL size/density pattern, remnant lipoprotein cholesterol expressed as IDL-C + small VLDL-C and HDL and LDL subclasses. The VAP folks claim that we misclassify LDL levels often (estimated at 50% of the time) based on the Friedewald equation. (even in face of small triglyceride elevations).
Specifically, they suggest that we could all do a much better job in choosing therapy. I.e., since IDL-C is only modestly statin responsive, we should use Statin plus niacin or fibrate whereas R-LDL-C is highly sensitive to statins.
They compare their VAP results to GGE(gel gradient electrophoresis), which is the gold standard and claim it correlates very well. They also tell us that "Probable Metabolic Syndrome" can be diagnosed earlier and more efficiently when low HDL, high TG and small/dense LDL pattern B are all coexistant. I guess my "coke and candy-bar test" with 1 hour and 2 hour post prandials is not scientific enough when you look at the bulk of this lipidology info.
For more information, you can check the website, www.thevaptest.com or call 1-800-719-9807. Cost: 244.00$ US dollars vs. standard lipid panel 87.00$.
I'd love it if some of our lipidologists would weigh in on this question and put in their HDL's worth! Dan, I hope this helps. I only wish I could tell you what the heck VAP stands for!!!
Melissa |
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April 25, 2005 11:10 (EDT)
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going beyond LDL in risk prediction..
Thanks for the info, Melissa. I think there are enough data now to support measuring apolipoproteins and not just performing the cursory gross HDL / LDL calculation. That is, measurement of particle size and apolipoprotein components to better fine-tune risk (see the INTERHEART study). I had not heard of VAP and wonder if this technology is available in Canada. |
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April 26, 2005 01:58 (EDT)
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statin myalgia
Melissa, have you tried Co-Enzyme Q-10 supplementation with your low-dose statin to help with the myalgias? It is used regularly in folks with muscle-wasting neurodegenerative diseases (ie, ALS) to help with cramping. Someone did a small study using it in statin-related myalgias and had a poster at ACC (I forget who it was). These were folks with mild CK elevations, no frank myopathy (that is, weakness) and no rhabdo, just annoying myalgias. In their small study, folks got considerable relief, such that a number were able to stay on their statin when they were about to stop it altogether. Granted, this was a single-center small unblinded study, but maybe it's something. Just a thought. |
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April 26, 2005 03:27 (EDT)
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standard lipid panel best?
Author
Tzou, Wendy S. MD; Douglas, Pamela S. MD; Srinivasan, Sathanur R. PhD; Chen, Wei MD, PhD; Berenson, Gerald MD; Stein, James H. MD
Institution
From University of Wisconsin Medical School, Madison, Wisconsin; Duke University Medical Center, Durham, North Carolina; and Tulane University Health Sciences Center, New Orleans, Louisiana.
Title
Advanced Lipoprotein Testing Does Not Improve Identification of Subclinical Atherosclerosis in Young Adults: The Bogalusa Heart Study.[Article]
Source
Annals of Internal Medicine. 142(9):742-750, May 3, 2005.
Abstract
Background: The clinical value of advanced lipoprotein testing relative to traditional lipid testing remains controversial. To date, no studies have evaluated associations between advanced lipoprotein testing and subclinical atherosclerosis in healthy young adults.
Objective: To determine whether advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation better predicts carotid intima-media thickness, a validated measure of subclinical atherosclerosis, than does traditional lipoprotein testing in asymptomatic young adults.
Design: Cross-sectional community-based study.
Setting: Bogalusa, Louisiana.
Participants: 311 randomly selected adults from the Bogalusa Heart Study who were 20 to 38 years of age.
Measurements: The authors performed advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation, traditional testing using enzymatic methods, and Friedewald formula estimation of low-density lipoprotein cholesterol levels. A certified reader blinded to lipoprotein results determined carotid intima-media thickness by B-mode ultrasonography. C-statistics from area under the receiver-operating characteristic curves (AUCs) derived from multivariable regression models were compared.
Results: Lipid values obtained with advanced lipoprotein testing did not predict carotid intima-media thickness better than traditionally measured lipid values in 236 participants for whom all data were available. A model using traditional lipoprotein measures (AUC, 0.754 [95% CI, 0.690 to 0.812]) did not differ significantly from a model using advanced lipoprotein measures (AUC, 0.779 [CI, 0.662 to 0.871]) for prediction of carotid intima-media thickness (P > 0.2). Subclass pattern of LDL, lipoprotein(a) cholesterol, intermediate-density lipoprotein cholesterol, high-density lipoprotein cholesterol subclasses, and very-low-density lipoprotein subclasses did not improve the performance of models for prediction of carotid intima-media thickness.
Limitations: The study was cross-sectional, cardiac events were not determined, and only 1 method of advanced lipoprotein testing was used.
Conclusions: Advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation did not improve prediction of carotid intima-media thickness in young adults and may not be useful for assessing cardiovascular risk in this population. |
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April 27, 2005 09:57 (EDT)
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Sooooo.......
All the $500 words (like my dad was so fond of saying when i would try them out on him during school) are saying "Go back to the Garden of Eden, eat what God intended the human body to eat, exercise by just working that body He gave you, and you'll be fine"!!! Now, can somebody figure out a magic spell or pill to MAKE me do this??!! I'm afraid I (and the rest of us, most likely) can lecture all day on these wonders, but if we don't have the will-power to actually DO them, it's all for naught! I can't take statins at any level, and wonder if Questran (good ole powder) would do the trick? That, and lots of water, and exercise, and good whole wholesome food and.... ;-} |
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April 27, 2005 02:51 (EDT)
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Advanced lipid testing
I reserve VAP testing for borderline cases I'm considerng pharmacologic therapy for and those in whom I'm on the fence about dual therapy. If the TG is sufficiently high, we can assume small LDL and go to dual. Also, young patients with a high-risk family history, despite that one study cited.
I'm curious if Melissa has used Zetia or niacin.
As far as diet, the studies and media have done nothing more than confuse the lay (and nonlay?) population. The only consistent data I've seen favors a Mediterranean diet. |
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April 28, 2005 09:11 (EDT)
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great discussion
Thanks to all of you guys for a great discussion, and I am very grateful for all of your suggestions.
First of all, I did try CoQ 10 for a couple of weeks, and to did seem to tolerate my ultra low zocor 5 mg dose better, but for whatever reason, I think lack of good controlled randomized trials, I thought, this is crazy, I'm not certain what this stuff might be doing to me, so I stopped, then the muscle aches started. So, I'm thinking it might have helped, and I might try it again.
I did zetia, three times now and each time at week three, I got a headache. I don't have a headache often, so I think it's related, and I stopped.(couldn't find this reported anywhere) I've been amazed as I've stated on prior posts at the dramatic drops in Lpa that I see with this drug on occasion, especialy since Niacin is the only drug that is supposed to impact Lpa.
I've not tried Niacin.
So, I'm a fish oil person, now on my third bottle and I do so love the Mediterranean diet, minus the wine (breast cancer risk). I exercise my guts out every day and hope for the best.
Thanks again to everyone for your commentary.
Melissa
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Heart Wire: Omega 3's show benefit in post op afib
It's a small study, but fascinating that it demonstrated >50% reduction in post op afib when pts were treated for 7 days prior to surgery with Omega 3's. . Valvular and prior atrial arrythmia patients were excluded.
Wonder if this will be reproducible when a larger scale trial is performed? Should be Easy enough to do with a low side effect profile I would think.
Melissa |
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