Thiazides and Beta-blockers and VLDL/HDL

[unsung]

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Ok guys... I'm abandoning the "pharmacologic treatment" vs "non-pharmacologic treatment" debate for now, 'cuz I really want to know this... hence the new thread 😉

So... beta-blockers increase risk for diabetes, we all know this. But on a more basic mechanistic level, what's really going on is that beta-blockers (AND thiazides) both inhibit lipoprotein lipase in capillaries --> which leads to (+) VLDL = acquired hypertriglyceridemia.

AND, we all know that (+) VLDL essentially corresponds to a (-) HDL. And HDL is really the predictive marker for future adverse events (as opposed to LDL).

Therefore, doesn't it follow that taking thiazides "prophylactically" for mild hypertension (or beta-blockers in whatever way you want-- either as HTN tx, which I guess you're not supposed to do anymore, at least for 1st line... or to tx HF) actually leads to worse lipid profile and increased risk of coronary artery disease/peripheral arterial disease, in the long-term?

So, please explain to me the rationale behind someone who is pre-hypertensive or *mildly* hypertensive starting on a thiazide diuretic (which basically needs to be continued indefinitely) as a preventive measure. Yeah, it will decrease sodium/water retention and thus prevent high BP... but it's also screwing up the lipid profiles for long-term heart health. And, I really don't see any way around this. 'Cuz when thiazides are given *prophylactically*, doesn't the pt have to keep taking them?

Why would you want to do this?? (Also, if any residents, etc. with more experience are reading this, I would like to know your experience with these drugs as well... because at least theoretically, this doesn't seem to jive.)

 

[OveractiveBrain]

A classic demonstration of the link between basic sciences (which I assume is where you are in your education) and clinical medicine.

By reading a series of side effects and contradndications mangled with indication and drug names, the true impact of medicine is lost. I'm not even sure your "we all know" comments are readily appropriate, and frankly, your logic is a bit flawed. It seems as though you are following your own education or are focusing on nuances discussed in a pharmacology class.

Arguement 1: "can" does mean "does." The reality of the matter is that people managed for hypertension with a thiazide diuretic requires monitoring for their potassium, not their dysplipidemia. In fact, patients are screened for dyslipidemia because of cardiac risk, not because they are put on a thiazide or beta blocker. That means while you may learn a drug CAN do something, it does not mean it DOES do it in EVERYONE. In addition, moving the lipid profile around doesn't represent an increased risk from dyslipidemia. What's the start point? How much does it change?

Saying that Beta Blockers and Thiazides induce acquired dyslipidemia is just wrong. They CAN, they MIGHT, and to a CERTAIN EXTENT.

Argument 2: MOrtality / Morbidity benefit
The good that comes of staving off long term hypertension is greater than any potential bad. Evidenced based medicine (not simply relying basic science predictions) has said its a good thing, so we do it. Decades worth of cardiology research in real people show a clear benefit.

Furthermore, "prophylaxis" for patients who are pre-HTN should be with ACE-i or ARBs. Thiazides are front line therapy for Stage I hypertension. They are gentle anti-hypertensives in patients who need additional help to diet and exercise (both, when successfully performed, reduce systolic BP by about 5mmHg each).

Argument 3: Beta Blockers are not front line HTN
Beta-Blockers are great for heart failure or post myocardial infarction, but they are not considered useful for BP control. Thiazides, ACE/ARB, CCB are all recommended above BB, unless there is a specific reason to be on a BB (like post MI) or in the setting of heart failure.

Argument 4:Beta Blockers may be hazardous in DM, not cause it:
One sign or symptom of hypoglycemia is tachycardia; beta blockers prevent those findings. Mild elevations of blood sugars or LDL, through whatever mechanism you want, do not induce diabetes. So true is this fact that Beta Blockers are started in a Diabetic who has heart failure and HTN; the mortality benefit far exceeds any downside from diabetes. Obviously, in the setting of comorbid conditions (i.e. DM), better medications are available (like ACE-i / ARB)

In short mortality and morbidity improve (it works) and evidenced based medicine is stronger than basic science prediction (dont rely on basic sciences to drive your medical decision making).

 

[Dirt]

Ok guys... I'm abandoning the "pharmacologic treatment" vs "non-pharmacologic treatment" debate for now, 'cuz I really want to know this... hence the new thread 😉

So... beta-blockers increase risk for diabetes, we all know this. But on a more basic mechanistic level, what's really going on is that beta-blockers (AND thiazides) both inhibit lipoprotein lipase in capillaries --> which leads to (+) VLDL = acquired hypertriglyceridemia.

AND, we all know that (+) VLDL essentially corresponds to a (-) HDL. And HDL is really the predictive marker for future adverse events (as opposed to LDL).

Therefore, doesn't it follow that taking thiazides "prophylactically" for mild hypertension (or beta-blockers in whatever way you want-- either as HTN tx, which I guess you're not supposed to do anymore, at least for 1st line... or to tx HF) actually leads to worse lipid profile and increased risk of coronary artery disease/peripheral arterial disease, in the long-term?

So, please explain to me the rationale behind someone who is pre-hypertensive or *mildly* hypertensive starting on a thiazide diuretic (which basically needs to be continued indefinitely) as a preventive measure. Yeah, it will decrease sodium/water retention and thus prevent high BP... but it's also screwing up the lipid profiles for long-term heart health. And, I really don't see any way around this. 'Cuz when thiazides are given *prophylactically*, doesn't the pt have to keep taking them?

Why would you want to do this?? (Also, if any residents, etc. with more experience are reading this, I would like to know your experience with these drugs as well... because at least theoretically, this doesn't seem to jive.)

Your logic is not supported by the literature.

Also you would be hard pressed to find someone who would "prophylactically" treat pre-hypertension or mild hypertension, which does not even really make sense.

You treat hypertension, which, in a sense, is prophylaxis against the deleterious effects of longstanding hypertension that are severe and often irreversible once they happen.

What you fail to see is the big picture. You must weigh the costs of treatment (or lack thereof) with the benefits. In this case, the costs of treatment are minuscule compared to the benefits of preventing stroke, MI, CHF, etc... the incidence of which are without a doubt prevented by blood pressure control.

 

[werd]

A classic demonstration of the link between basic sciences (which I assume is where you are in your education) and clinical medicine.

By reading a series of side effects and contradndications mangled with indication and drug names, the true impact of medicine is lost. I'm not even sure your "we all know" comments are readily appropriate, and frankly, your logic is a bit flawed. It seems as though you are following your own education or are focusing on nuances discussed in a pharmacology class.

Arguement 1: "can" does mean "does." The reality of the matter is that people managed for hypertension with a thiazide diuretic requires monitoring for their potassium, not their dysplipidemia. In fact, patients are screened for dyslipidemia because of cardiac risk, not because they are put on a thiazide or beta blocker. That means while you may learn a drug CAN do something, it does not mean it DOES do it in EVERYONE. In addition, moving the lipid profile around doesn't represent an increased risk from dyslipidemia. What's the start point? How much does it change?

Saying that Beta Blockers and Thiazides induce acquired dyslipidemia is just wrong. They CAN, they MIGHT, and to a CERTAIN EXTENT.

Argument 2: MOrtality / Morbidity benefit
The good that comes of staving off long term hypertension is greater than any potential bad. Evidenced based medicine (not simply relying basic science predictions) has said its a good thing, so we do it. Decades worth of cardiology research in real people show a clear benefit.

Furthermore, "prophylaxis" for patients who are pre-HTN should be with ACE-i or ARBs. Thiazides are front line therapy for Stage I hypertension. They are gentle anti-hypertensives in patients who need additional help to diet and exercise (both, when successfully performed, reduce systolic BP by about 5mmHg each).

Argument 3: Beta Blockers are not front line HTN
Beta-Blockers are great for heart failure or post myocardial infarction, but they are not considered useful for BP control. Thiazides, ACE/ARB, CCB are all recommended above BB, unless there is a specific reason to be on a BB (like post MI) or in the setting of heart failure.

Argument 4:Beta Blockers may be hazardous in DM, not cause it:
One sign or symptom of hypoglycemia is tachycardia; beta blockers prevent those findings. Mild elevations of blood sugars or LDL, through whatever mechanism you want, do not induce diabetes. So true is this fact that Beta Blockers are started in a Diabetic who has heart failure and HTN; the mortality benefit far exceeds any downside from diabetes. Obviously, in the setting of comorbid conditions (i.e. DM), better medications are available (like ACE-i / ARB)

In short mortality and morbidity improve (it works) and evidenced based medicine is stronger than basic science prediction (dont rely on basic sciences to drive your medical decision making).

pretty much this. you're stream of "we all know," "essentially," and "is really" adds up to create a false pretense. you can argue mechanisms and theoreticals but the evidence shows that thiazides and other BP meds like beta blockers help people with hypertension more than they hurt. i also question a lot of your associations and assertions about the effects of these meds on lipids and other areas of metabolism... i think the interactions are weak, rare, and in most patients academic rather than being of real significance. i suspect clinical experience will assuage many of your concerns.

 

[unsung]

FIRST... disclaimer: Yes, more actual "clinical" experience will likely assuage all my recent concerns. 😉 So, I get your guys' main point.

That said...

A classic demonstration of the link between basic sciences (which I assume is where you are in your education) and clinical medicine.

By reading a series of side effects and contradndications mangled with indication and drug names, the true impact of medicine is lost. I'm not even sure your "we all know" comments are readily appropriate, and frankly, your logic is a bit flawed. It seems as though you are following your own education or are focusing on nuances discussed in a pharmacology class.

Arguement 1: "can" does mean "does." The reality of the matter is that people managed for hypertension with a thiazide diuretic requires monitoring for their potassium, not their dysplipidemia. In fact, patients are screened for dyslipidemia because of cardiac risk, not because they are put on a thiazide or beta blocker. That means while you may learn a drug CAN do something, it does not mean it DOES do it in EVERYONE. In addition, moving the lipid profile around doesn't represent an increased risk from dyslipidemia. What's the start point? How much does it change?

Saying that Beta Blockers and Thiazides induce acquired dyslipidemia is just wrong. They CAN, they MIGHT, and to a CERTAIN EXTENT.

They DO induce (+) VLDL. Not "can", "might". Yeah, I don't know to what extent... which is why I made this post, actually.

Raising the VLDL a bit probably doesn't cause any acute problems. Presumably this is why monitoring patients for this is pointless. (Unlike messing around with potassium levels, which can lead to acute arrhythmias or what not. You'd know more than I.)

But what I'm wondering about is the long-term effects. And assuming that long-term mildly elevated VLDL (or mildly lowered HDL) has no effects doesn't seem reasonable to me.

Argument 2: MOrtality / Morbidity benefit
The good that comes of staving off long term hypertension is greater than any potential bad. Evidenced based medicine (not simply relying basic science predictions) has said its a good thing, so we do it. Decades worth of cardiology research in real people show a clear benefit.
Furthermore, "prophylaxis" for patients who are pre-HTN should be with ACE-i or ARBs. Thiazides are front line therapy for Stage I hypertension. They are gentle anti-hypertensives in patients who need additional help to diet and exercise (both, when successfully performed, reduce systolic BP by about 5mmHg each).

This is probably the strongest point 😉

Goes with the whole idea of "clinical thinking" of benefits outweighing the side effects. So I can believe that for majority (or even vast majority) of patients, my OP is entirely null & pointless. And the post before that on lifestyle modifications. 🙄 Assuming your "average" patient is overweight, resistant to making any lifestyle changes, etc. and so on.

...*Probably* not too concerned that thiazides are messing up lipid profile long-term... the lipid profile is probably already messed up. 🙄

Argument 3: Beta Blockers are not front line HTN
Beta-Blockers are great for heart failure or post myocardial infarction, but they are not considered useful for BP control. Thiazides, ACE/ARB, CCB are all recommended above BB, unless there is a specific reason to be on a BB (like post MI) or in the setting of heart failure.

Beta-blockers aren't front-line. Especially not supposed to be front-line, anyway, by JNC 7 guidelines. I think I get this point now. No argument there... lol

Argument 4:Beta Blockers may be hazardous in DM, not cause it:
One sign or symptom of hypoglycemia is tachycardia; beta blockers prevent those findings. Mild elevations of blood sugars or LDL, through whatever mechanism you want, do not induce diabetes. So true is this fact that Beta Blockers are started in a Diabetic who has heart failure and HTN; the mortality benefit far exceeds any downside from diabetes. Obviously, in the setting of comorbid conditions (i.e. DM), better medications are available (like ACE-i / ARB)

In short mortality and morbidity improve (it works) and evidenced based medicine is stronger than basic science prediction (dont rely on basic sciences to drive your medical decision making).

What you're saying about beta-blockers masking hypoglycemia symptoms is true.

BUT it's has nothing do with what I said about beta-blockers (think decades of use) actually increasing risk of developing diabetes. It also increases cardiovascular events like stroke. There is a reason why beta-blockers aren't considered front line drugs for hypertension anymore, after all. (Independent from better drugs being available.)

Basically, I get your point about the "gulf" between basic science & "evidence-based medicine". Especially the bit about benefits >> risks. After all, that's how clinical practice operates, isn't it? There's always side effects... I guess I will have to make peace with that.

But, dude, no one actually answered my original Q. Call it an academic concern, if you want.

Yet... SDN, I expected more from you!! 😎

P.S. I don't see the harm in thinking from a basic science "perspective"... presumably if the drugs have been empirically used for years and shown to be of benefit empirically, there exists some basic science explanation why what I originally posted is inapplicable. What's most likely is that I'm just not understanding the science well enough or misunderstanding it.

So, if what I said was false or irrelevant in some way (e.g. effect of thiazides on VLDL is too small to be important)... please point it out to me. 'Cuz I'd still like to know.

 

[OveractiveBrain]

So, please explain to me the rationale behind someone who is pre-hypertensive or *mildly* hypertensive starting on a thiazide diuretic (which basically needs to be continued indefinitely) as a preventive measure. Yeah, it will decrease sodium/water retention and thus prevent high BP... but it's also screwing up the lipid profiles for long-term heart health. And, I really don't see any way around this. 'Cuz when thiazides are given *prophylactically*, doesn't the pt have to keep taking them?

This was your original question. Perhpas not answered as explicitly as you would have hoped, but answered.

OP DIRECT ANSWER:
The rationale is that the morbidity and mortality benefit supercede and risk. That means (perhaps you dont understand that statement) that putting people on medications "prophylactically" or "at all" is better than not doing it "prevent high BP". But your assumption that is "screwing up the lipid profile" is not valid. For one, It doesn't screw up "their" lipid profiles, it might only contribute to dyslipidemia in some patients. For two, the degree to which it "screws up" the lipid profile varies, and in most cases, in no meaningful manner.

Take a step back, realize that your assumptions are assumptions of totality, and are not assumptions to be made. Yes a patient keeps taking medications once started. No they do not contribute to diabetes or dyslipidemia. If someone is sick enough to start an anti-hypertensive at 30 years old, then 40 years later they are probably going to have diabetes and dyslipidemia not because of a side effect of a thiazide, but because of a lifetime of poor diet, miserable exercise, and general bad habits. Attributing their long term chronic disease to the initiation of a medication (in this case) is simply erroneous. Realize that not every reaction listed in epocrates actually happens to everyone. Severe risk, or things that happen often, make it onto black box warnings, not listed as drug reactions.

To answer the question in the last post, what's wrong with looking at medicine from a basic science perspective, take a look at the italics.

What is, right now, one of the most used medications in heart failure? Beta blockers. What do beta-blockers do? Well, they are negative inotropes. The weaken the heart. They are negative chronotropes, they make the heart weaker. Basic science principles said NEVER USE BB IN HEART FAILURE. We had beta blockers for decades, and we never used them. Why not? Basic science said we would take a weakened heart, compensating with tachycardia and slow it down and weaken it. Why would we do it?

Bam. Someone decided to try it. Whoops. Beta Blockers improve heart failure. Retrospectively we argue that the decrease in heart rate allows adequate filling, afterload is reduced, and the heart doesn't have to work as hard, so actually does better. We ASSUMED basic science was correct. But did we try it? Not for a long ass time. Now we know beta blockers are excellent in heart failure, especially after a myocardial infarction

That's whats wrong with basic science perspective directing clinical decisions. The theoretical is rarely the actual. And until a medication or intervention has been tested time and time again, in multiple people, in multiple populations, you can't possibly predict the behavior with simple basic science principles. Basic sciences eliminate most of the complexity of a human body, reduce the system to pluses and minuses. We gain significant insight from basic science, they are incredibly important. But you are going to be a doctor. While comprehending fundamentals (the purpose of the basic science curriculum) is essential, the fundamentals lay the ground work for working through problems to which you apply the current recommendations, not directing your medical decision making.

Basic science curriculum implants the foundation for comprehension of disease and therapy, not directing medical decision making. Medical decision making is a constantly transforming field based on new evidence.

 

[J ROD]

Beta blockers causing depression is another thing to think about...

 

[mjl1717]

Yes, one of the big things.. What you read about in the books and what actually happens in real - time medicine is often two different things!