nose@nbires.UUCP (Steve Dunn) (11/13/85)
Steve Dyer in a recent article said that thiazide diuretics (Used to treat
hypertension) are associated with a rise of 5% in the cholesterol level,
10% in total triglycerides and 10% in low density lipoproteins. He also
says that the clinical signficance of this is unknown.
First I wonder if anyone knows what the normal values for these items
are and what is considered too high. This might help in guessing whether
5 or 10% rises are significant.
Second I wonder if a person using thiazides should be tested for these
things.
Third if Steve has a reference for the increase blood lipid findings I'd
really like to get it.
Fourth a friend of mine told me that she had heard that diuretic use had
recently been associated with an increased risk of heart attack even
when compared with no treatment at all. I don't believe it but I wonder
if there has been any finding like this. It could be merely a distortion
of the findings Steve Dyer reported.
Any answers would be greatly appreciated!
-Steve "Brain? Sorry, wrong planet." Dunnsdyer@bbnccv.UUCP (Steve Dyer) (11/14/85)
> Third if Steve has a reference for the increase blood lipid findings I'd > really like to get it. Goldman, A. I., et. al., Serum lipoprotein levels during chlorthalidone therapy. J.A.M.A., 1980, 244, 1691-1695. Grimm, R. H., et. al., Effects of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive patients. Ann. Intern. Med., 1981, 94, 7-11. Perez-Stable, E., and Caralis, P. V., Thiazide-induced disturbances in carbohydrate, lipid and potassium metabolism. Am. Heart J., 1983, 106, 245-251. There is some evidence that concomitant administration of beta-adrenergic blockers prevents the increase in serum lipids. Meier, A, et. al., Reversal or prevention of diuretic-induced alterations in serum lipoproteins with betablockers. Atherosclerosis, 1982, 41, 415-419. Weidmann, P., et. al., Effects of antihypertensive therapy on serum lipoproteins. Hypertension, 1983, 5, Suppl. III, 120-131. -- /Steve Dyer {decvax,linus,ima,ihnp4}!bbncca!sdyer sdyer@bbnccv.ARPA
werner@aecom.UUCP (Craig Werner) (11/15/85)
> First I wonder if anyone knows what the normal values for these items > are and what is considered too high. This might help in guessing whether > 5 or 10% rises are significant. Normal is actually too high. It varies from lab to lab. And since risk in directly (and exponentially) related to blood levels, any increase is significant. > Third if Steve has a reference for the increase blood lipid findings I'd > really like to get it. It's in the package insert (and required to be there) on all drugs that it is associated with, also on all the ads in Medical Journals. Not to mention the PDR and Merck manual, which Steve Dyer is exquisitely consistent in consulting. There are now coming on the market several brands of diuretics that do not raise lipids at all, and will be many more if they sell well. > Fourth a friend of mine told me that she had heard that diuretic use had > recently been associated with an increased risk of heart attack even > when compared with no treatment at all. I don't believe it but I wonder > if there has been any finding like this. To repeat, according to MRFIT, Diuretic use in patients with borderline hypertension (90-95 diastolic) and existing cardiac arrythmias (EKG abnormalities) can aggravate this and lead to an increased risk of sudden death. The mechanism is loss of Potassium with the Sodium. These patients should be (and are) put on Potassium-sparing diuretics instead. If no such electrical abnormality exists, then there is no risk. Or, if blood pressure is higher, the risk of BP complication far exceeds the added risk (which is now avoided in current practice -- after all, doctors read these studies too, you know.) --
wurzelma@aecom.UUCP (John Wurzelmann) (11/16/85)
> > To repeat, according to MRFIT, Diuretic use in patients with > borderline hypertension (90-95 diastolic) and existing cardiac arrythmias > (EKG abnormalities) can aggravate this and lead to an increased risk of > sudden death. The mechanism is loss of Potassium with the Sodium. These > patients should be (and are) put on Potassium-sparing diuretics instead. > If no such electrical abnormality exists, then there is no risk. Or, if > blood pressure is higher, the risk of BP complication far exceeds the added > risk (which is now avoided in current practice -- after all, doctors read > these studies too, you know.) > Craig, the M.R.F.I.T. study does hint at the conclusions which you summarize, but it does not state them with anywhere near the conviction that you do. Rather the M.R.F.I.T. study offers the above notion as a hypothesis to explain the relatively small excess of deaths which occurred in the intensively treated study group. This hypothesis is by no means proved and should not be forth as fact. Sincerely, John Wurzelmann
sdyer@bbnccv.UUCP (Steve Dyer) (11/17/85)
>> Third if Steve has a reference for the increase blood lipid findings I'd >> really like to get it. > It's in the package insert (and required to be there) on all drugs that > it is associated with, also on all the ads in Medical Journals. Not to > mention the PDR and Merck manual, which Steve Dyer is exquisitely consistent > in consulting. Actually, the Merck Manual doesn't mention thiazide-induced increases in blood lipids, and I don't own a PDR. The latest 1985 Goodman and Gilman mentions this, and the references I posted were transcribed from a computerized literature search on "Paperchase", Beth Israel's medical database service. Regarding new diuretic agents which may not produce this increase in blood lipids, they may eventually be welcomed into a doctor's armamentarium, but as a medical consumer, you might want to ask yourself whether you'd prefer to be treated with agents which have been in use for billions of patient-years, instead of the "latest" drug, which of necessity is much less familiar and which may have undiscovered side-effects. (Provided that these older agents are effective and do not cause you undesirable side-effects.) Certainly it is prudent to measure a patient's lipids if thiazides are being given, but if the drug-induced increase is small, it doesn't necessarily follow that one MUST change to a new diuretic. I mention this specifically in the context of thiazide diuretics and their well-known actions, because about 5 or 6 years ago, a new diuretic, ticrynafen, was promoted as specifically avoiding another side-effect of thiazide therapy, retention of uric acid, which may aggravate gout in susceptible individuals. Indeed, it actually promoted the excretion of uric acid, much like some drugs used only for gout. Ticrynafen became quite popular when it was introduced and many patients were treated with this drug, even though they might not have been at risk for gout, and whose thiazide-induced hyperuricemia might have been clinically insignificant (or non-existent, assuming that they went directly on ticrynafen.) It turned out that a significant proportion of those receiving ticrynafen (0.01 - 0.1 %) suffered from varying degrees of liver toxicity, an effect which wasn't uncovered until it was approved and in wide use. It was quickly withdrawn by the FDA, much to the chagrin of Smith, Kline and French stockholders. All this points to just a simple fact: that prescribing a therapy isn't simple, that there are always tradeoffs which the physician and patient have to come to terms with, and that the yet-unknown offers as many uncertainties as the knowledge which we are developing. -- /Steve Dyer {decvax,linus,ima,ihnp4}!bbncca!sdyer sdyer@bbnccv.ARPA