Blood pressure medications and prostate cancer

[Graham49]

pjoshea posted on this after the Barcelona conference. The full paper is now available via Google Scholar.

Here are some extracts. Antihypertensive drugs and prostate cancer survival after radical prostatectomy in Finland – a nationwide cohort study

Eerik EE Santala1, Antti Rannikko2, Teemu J Murtola1,3*

1 University of Tampere, Faculty of Medicine and Life Sciences, Tampere, Finland

2 Department of Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland 3 Tampere University Hospital, Department of Urology, Tampere, Finland

Abstract

Antihypertensive (anti‐HT) drugs targeting renin‐angiotensin‐aldosterone (RAA)‐ system have been associated with improved prostate cancer (PCa)‐specific survival. Challenge is that often multiple drugs are used simultaneously. We evaluated the association between use of anti‐HT drugs and PCa survival among 14,422 surgically treated Finnish PCa patients. Information on drug purchases was obtained from a national prescription database. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of PCa death and initiation of androgen deprivation therapy (ADT) with adjustment for age, tumor extent, use of statins and for Charlson Comorbidity Index. Angiotensin‐converting enzyme (ACE)‐ inhibitors, angiotensin‐ receptor (ATR)‐blockers, diuretics, calcium‐channel blockers, beta‐blockers and other anti‐HT drugs were analyzed as separate time‐dependent variables to model simultaneous use. Overall anti‐HT drugs were associated with an increased risk of PCa death. Conversely use of ATR‐blockers was associated with decreased risk of PCa death (HR: 0.43, 95% CI: 0.26–0.72 and HR: 0.60, 95% CI 0.37–0.97 for pre‐ and post‐diagnostic use). Similar risk decrease was not observed in other drug groups. Anti‐HT drugs were also associated with an increased risk of starting ADT, with the exception of ATR‐blockers (HR: 0.81 CI:0.71–0.92). ATR‐ blockers differ from other anti‐HT drugs as the survival is better in users of this drug group. The result partly supports the role of RAA system in PCa progression. Nevertheless, the risk decrease was not observed in ACE‐inhibitor users. Further research is needed to elucidate the molecular mechanism for the potential anticancer effect of ATR‐ blockers.

In conclusion, antihypertensive drugs are associated with increased risk of PCa death and starting of ADT after radical prostatectomy. An exception are ATR-blockers which are associated with better PCa survival and lowered risk of starting ADT. The risk decrease is observed in inverse association with annual dose of ATR-blocker use. Our results support further studies elucidating the mechanism behind the possible anticancer effect, and ultimately doing clinical trials testing ATR-blockers in men with prostate cancer.

[cesanon]

Graham, what do you search for to find this study on Google Scholar?

I would like to give it to my nephrologist to have him recalibrate the hypertension drug mix that he has me on.

[Graham49 in reply to cesanon]

Cesanon, search on "anti hypertensive drugs and prostate cancer survival" then clic on pdf near the top right corner of the abstract

[Graham49 in reply to cesanon]

Cesanon, just noticed that you used the word "nephrologist". I also have a nephrologist. I had a kidney transplant in 2016.

[GeorgesCalvez]

Moi aussi, I saw the abstract, I am taking Irbesartan which is an ARB.

[Graham49 in reply to GeorgesCalvez]

George, in the 2016 paper "The different therapeutic choices with ARBs which one to give? When? Why?" It says that Irbesartan was found to improve erectile dysfunction after radical prostatectomy. Can you confirm this for your case?

[Graham49]

Yes, but all the ARBs and ACE inhibitors relax the arteries.

[Stegosaurus37]

Um, Bernoulli works the other way. When you restrict the flow, the pressure decreases, but the flow speeds up. It's why aircraft can fly. The increased camber on the top of the wing causes the airflow to speed up decreasing the pressure on the top of the wing. This creates lift and the aircraft goes up. I've got 2200 hours of flying time because it works this way.

[Gearhead in reply to Stegosaurus37]

I absolutely respect and admire your flying experience. But that explanation of how a wing works is pretty much an urban myth. If that were the case, how come airplanes can fly upside down? There is no equivalently simple accurate answer other than: a wing creates lift by deflecting the momentum of the air downward. The most accurate answer gets into circulation. Apologies for the off-topic nit.

And Bernoulli's equation applies to inviscid fluids; momentum forces >> viscous forces. But for blood in arteries, viscous forces are substantial. Better to think of as pipe flow with friction, which requires increased pressure to overcome.

[Hidden in reply to Gearhead]

I like off topic discussions. Because of this crap I’ve met some amazing and brilliant people. You guys keep it up. I’ll just enjoy.

[Stegosaurus37 in reply to Gearhead]

It's called "G" - equivalent to the force of gravity. When you are turning the aircraft, level or vertical,, you are applying "G" forces. To make a 60 degree bank, level turn, you need to apply 2 "G". In so doing you are increasing the effective camber of the wing and so increasing the "lift". (If you run across the expression "angle of attack", this is what they are talking about.) That's simple physics. Yes, the force of gravity - commonly known as "God's G" is acting but that just complicates the equation. In simplest terms, the amount of "G" you are putting on the aircraft determines its effective lift; your orientation to the earth's surface is irrelevant. (My sister-in-law couldn't understand why I could perform an aileron roll and not fall out. My wife thought it was because I was strapped in. Gadzooks.)

There are diagrams to explain how Bernoulli acts to create "lift", but I can't seem to get them to copy. So, simplest is to consider a wind tunnel. The "wing" model is held stationary and the air flows over it. The bottom of the wing is straight so the air flow goes right along it. The top is curved, so the airflow has to speed up. As it speeds up, Bernoulli causes the pressure against the top of the wing to decrease while the pressure against the bottom of the wing remains constant. The wing will then follow the path of least resistance and move up into the area of decreased pressure, moving the entire aircraft up so it flies.

In reality, of course, it's the wing that's moving and the air mass that's stationary, but the physics is equivalent ad it's conceptually easier to think of the wing as stationary and the air mass as moving.

This is a wildly simplified explanation; I hope I haven't confused you too much.

[j-o-h-n]

Geez... I think reading all of this has my pressure is rising... Wish my zip code was 12080.

Good Luck, Good Health and Good Humor.

J-o-h-n Monday 07/01/2019 12:25 PM DST

[Hidden]

Wow, thanks for this post!! I asked my doctor to switch me from max dose amlodipine to Telmisartan and I hope she says yes.

Here's the link to an abstract about Telmisartan and prostate cancer:

researchgate.net/publicatio...

[Ssiddy in reply to Hidden]

Hi. Please can you explain in very basic terms why that may be a good switch. My dad is on amlodipine. Thanks

[Hidden in reply to Ssiddy]

Because amlodipine does control the blood pressure, but does not fight the prostate cancer. Telmisartan has been shown to do both, control blood pressure, as well as fight the prostate cancer (at least I think that's what articles about it say).

[Hidden in reply to Ssiddy]

Oh, and sorry your dad has prostate cancer (presuming). I have three adult children, and it was a very difficult time just after the oncologist gave me my prognosis. My kid's were floored. How long has he known?

[Ssiddy in reply to Hidden]

Hi. Thanks Marc. He is 73 and has stage 4 Gleason 9 with Neuroendrocrine differentiation diagnosed in September 2014. He has had hormone therapy, Docetaxel, xtandi and now on cabazitaxel. Not sure how much these tweaks will make a difference to him but it’s worth me asking. The treatment is making him weak and tired but we had good news last week as a CT scan showed complete resolution of lymph node mets. My poor dad 😢. Was working full time as a London taxi driver and was forced to retire in a December. Now he has to rely on me to get out of his house.

[Hidden in reply to Ssiddy]

I had about the same, stage 4, Gleason 8, with bone met, spread to seminal vesicles, and suspected in lymph nodes. I just try and get as much into each specific day as I can, and add enjoyment anywhere I can find it. Me, I retired at 57 with everything going for me, and then diagnosed 2 years, 8 months later.

[Stegosaurus37]

Bernoulli is about restricting the flow, and the pressure on the side walls of the tube it is flowing through will decrease as the tube is restricted. You and I are talking about different things. You are talking about the pressure at the end of the tube; Bernoulli doesn't address that.

[Stegosaurus37]

Agreed. It's a cancer site.

[2dee]

Can you comment on "niFEDipine", a BP drug suggested to work with my Lisinopril (prinivil, zestril) to lower my BP since it has increased so much on Lupron.

2Dee

[Graham49 in reply to 2dee]

Nifedipine is a calcium channel blocker, Lisinopril is an ACE inhibitor. Neither of these drug types showed a prostate cancer survival advantage in the Finish study, only ARBs.

[2dee in reply to Graham49]

Thanks, can you comment on WHETHER you feel that Nifedipine will in any way compete with Lupron ADT and cause any side effects beyond the Finish study. I need to reduce my BP if possible to help with stroke and heart attack. I had a 6 way bypass in 2001.

I wasn't trying to determine if the Nifedipine would help reduce my mPCa though that would be a bonus.

2Dee

[Graham49 in reply to 2dee]

You best talk to your consultant. I am not a doctor. I was on ADT and Nifedipine before I had radical prostectomy. It worked fine. My PSA went down to 0.4 before I had the RP, but everybody is slightly different . I have asked to go on to an ARB.

[Ralph1966]

I am taking 50 mg Losartan daily since 8 years, PCa diagnosed 2017 G9 (4+5).

Hope this with the metformin and simvastatin (I am diabetic) help me servive and reach 80s. I am 53 and after RRP failed my urologest said you will leave 20+ with the help of radiation/hormonal therapy/chemotherapy etc etc..

Nobody knows for sure how this disease will progress as each of us and our individual cancers are different!

It is scary that we don't know what is hidden for each if us and we have to live with this disease for the rest of our lives!

[Ralph1966]

Prostate cancer is found among people who take Losartan, especially for people who are 60+ old , have been taking the drug for 2 - 5 years, also take medication Amlodipine, and have High blood cholesterol. This study is created by eHealthMe based on reports of 70,992 people who have side effects when taking Losartan from FDA, and is updated regularly.

70,992 people reported to have side effects when taking Losartan.

Among them, 108 people (0.15%) have Prostate cancer.

ehealthme.com/ds/losartan/p...

[Graham49 in reply to Ralph1966]

Thanks for the post. It would take a lot scrutiny and analysis of the data and the sources to draw any proper conclusions. It's not even clear how many of the 70,000 plus people who reported side effects were men.

[ImaSurvivor1]

People taking Losartan should check the manufacturer of their particular Rx and then check the recalls. At least two brands of Losartan have been recalled in the last few months because of contamination at the Chinese source of the medication. I don't know if other manufacturer's versions of Losartan are also made by the same Chinese factories or not, but at least two have been recalled.

[Hidden]

I got my doctor to switch me from Amlodipine to Losartan (non contaminated stuff). Interesting in my research, Amlodipine may interact with Zytiga. Also positive for ARB's, they may have side effect of elevated blood potassium level, and on Zytiga I have been constantly needing to take like 10000mg of potassium per day just to keep it from going to low.

[GeorgeGlass]

Nal, Do these ATRs widen the arteries or lower the flow of blood? I have coronary artery diseases (thought to have a correlation with prostate cancer), so I assume that widening my arteries and supplying more blood flow might reduce mortality/longevity as indicated in the study, or maybe it's due to reduced blood flow? I already have a normal BP so I might not be a good candidate for an ATR? From your message above, it looks like you are saying that the ATRs work similar to L-Arginine, which I take along with Citrulline. Would taking an ATR be more effective or a t least a more even distribution (time-release throughout the day and night than the arg/citru combo (1.5 g morning and 1.5g night)? I can PM you if you prefer. Its a fairly lengthy pontification.

[GeorgeGlass]

ATR-blockers like Losartan is what I was talking about. I got loose with my writing.

[Graham49 in reply to GeorgeGlass]

From Wikipedia:

Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists,[1] also known as angiotensin receptor blocker,[2][3] angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.[4]

George since you have low blood pressure anyway, I suggest you be careful what you take. It needs a doctors input. Each of these drug types have slightly different characteristics and half lives.

[GeorgeGlass in reply to Graham49]

Ya, Im not going to take the ATR blockers. I'll just keep using the amino acids in reasonable doses, and increase my natto intake with morning smoothies and natto-serra supplements, along with my 45-90mcg of k2 daily.