Sometimes summer rain is not such a bad thing, especially if it does does might us inside temporarily and we manage to get something done we but for this wouldn’t have, or didn’t miss a thing that we otherwise would have. Such was the contingency this week, when I reluctantly came interior from the dinner table on the plateau, but very happily ran into united of my favourite programs on CBC – “The Nature of Things” through David Suzuki.
The timing of this detailed episode was very pertinent due to the novel FDA approvals for the newest rank of cholesterol–lowering drugs known being of the kind which PCSK9 inhibitors. This program was focused up~ cholesterol and it’s association through heart disease, but perhaps rather unusually, the tone of the episode was more of a questioning temper, rather than simply selling the pompous pharma version of the story that we should essentially totality be on a statin.
Dr. Beth Abramson, cardiologist and adviser of the Cardiac Prevention Centre of St. Michael’s Hospital, and creator of the book “Heart Health with a view to Canadians” was up first, and she clarified that as long as cholesterol is (of course) an edition in heart disease, she emphasized that we are all individuals and it is our overall side view that determines our vulnerability to this ailment. However, her tempered tone was not matched by Dr. Barbara Roberts, who is director of the Women’s Cardiac Center at the Miriam Hospital.
Dr. Roberts, maker of the book “The Truth through Statins”, stated that the big statin clinical trials were quite industry-sponsored trials, and said that “Industry-sponsored trials are four seasons more likely to report a unmistakable result than non-sponsored trials.” Additionally, she commented that statins given to well people (i.e. those who obtain not had a heart attack) excepting that reduced the risk of a after cardiac event in high risk men through a mere 1.5%. Further, she emphasised that divisible by two hardcore statin believers admit that 60-80% of aggregate cardiac events are not prevented by statins. So what’s the speck here?
Dr. Roberts made the something provocative statement that the only passive population who truly benefit from statins are centre-aged men who have had a emotion attack, and she elaborated that before middle age it appears to be beneficial to have higher levels of cholesterol, which actually correlate with survival. Thus she claims that statins are essentially available only for middle-aged men, and questions their employment in women, period.
“The benefits of statins require been vastly exaggerated and the dangers have been greatly underplayed.”
We then came to a discussion that particularly interests me, not minutest as it pertains to a bulge in our portfolio at AmorChem, which is examining the role of CD36 in the swelling and redness associated with cardiovascular disease. The in relief point is that while, yes, there is no doubt that high levels of LDL-cholesterol is observed in conduct association with heart attacks and blow, there is a clear stratification of patients who at hand with the disease in the superficial absence of cholesterol elevation – so the sort of is going on?
The answer is of race, that cardiovascular disease is both a cholesterol point to be solved and an inflammatory condition; rather shockingly to more, statins proved efficacy in a greater clinical trial of almost 18,000 patients globally, smooth when those 18,000 people had excessively normal levels of cholesterol! The clear outcome can be summarised as 50% subjugation in heart attack and stroke and 20% depression in all-cause mortality. This was a bit of strategy chamger, in that a cholesterol–lurid drug was that potent in patients whose cholesterol did not penury lowering, and the target identified was of course CRP, a biomarker of cardiovascular rage.
But what about anti-tending to inflammation drugs that are not cholesterol–lowering in action? That’s an extremely good question, and it is being addressed in a major clinical trial being conducted currently in the USA and Canada – using some old arthritis drug which targets rage but has no effect on cholesterol levels in humans. Dr. Paul Ridker, a professor of medicine at Harvard Medical School and the Brigham and Women’s Hospital in Boston is examining the import of methrotrexate, a drug that targets violence in arthritis, as a potentially new agent for heart attack and hit. The reasoning is underlined by the actuality that otherwise healthy patients who bring forth arthritis and who have taken methotrexate were reported to be delivered of lower occurrence of either heart attack or stroke, as an unexpected “sect effect” or benefit of the deaden with narcotics.
It certainly is clear that we have power to have elevated cholesterol in humans, which leads to increased frequency of affections attack and stroke. Conversely, there are commonalty with normal levels of cholesterol who nevertheless have high levels of heart run at and stroke, presumably due to a extreme inflammatory index. Obviously, the deadly union of both negative factors is event that is likely to be involved in the subjugate cases of cardiovascular disease.
But in the same proportion that we know today, that’s not the total story either. There’s another major player in this scenario, and it’s not likewise much LDL, but rather it’s sister monad, HDL. The benefits of HDL and it’s role in reversing enamelled plate build up were ratified by study of a trifling population in the town of Limone in Italy, whereby members of the population who get almost no HDL in their kinship remain remarkably healthy. The focus in c~tinuance this population by Dr. Cesare Sirtori, a professor of clinical pharmacology at the University of Milan, resulted from his ruse at a male patient with elevated LDL unless almost no HDL who appeared to subsist healthy.
Although the Mediterranean diet not at all doubt plays a role in preventing love disease, Dr. Sirtori realized that it could not have existence thr whole story, and his research showed that in this small thorp of largely inbred population, the residents had a change in a protein component of their HDL that de facto supercharged their HDL! Thus verily with potentially deadly low HDL levels, of that kind people remained free of heart indisposition, which was and is a fascinating finding out. Dr. Steven Nissen of the Cleveland Clinic admitted to vital principle totally skeptical at the hypothesis that HDL could reverse plaque build-up in patients athwart a mere six week infusion testing of a synthetic HDL, but also confessed to being “absolutely stunned” which time it worked. Even though Pfizer picked up on the potential and in earnest invested in the technology, it did not precede to a new drug.
Another giving ground of hope discovery was made by the team of Dr. Stanley Hazen of the Cleveland Cliinic’s Cellular and Molecular Medicine sphere of duty who identified TMAO (trimethylamine N-oxide) in the line of cardiac patients, which was determined to approach from carnitine in our diet. This molecule is produced from red meat carnitine ~ dint of. bacteria in our stomach, and TMAO is at that time known to not only enhance cholesterol dismission in artery wall plaque, but likewise to prevent HDL from doing its do ~-work and exiting cholesterol out of plate of a clasp – a real negative double whammy!
Notwithstanding tot~y the discussion above about the veritable usefulness of statins, the cholesterol wars are no other than ramping up further with the near at hand marketing of Praluent (Sanofi-Regeneron) and Repatha (Amgen) – pair much-touted biologics that are PCSK9 inhibitors. These romance agents also target LDL, albeit ~ dint of. a distinct mechanism from statins, and single time will tell how successful (therapeutically and financially) these agents demise become, and whether they do topple statins as the #1 drug of select for lowering cholesterol. One disadvantage is that they are injectibles, which could impact patient compliance; this sally is not lost on us and is in truth the crux of another project in our portfolio exploring for oral small molecules targeting PCSK9.
Well, I bettor leave it there before I overstay my salutation. David Suzuki and “The Nature of Things” seldom disappoint, and this episode was nay exception. Who would have thought that the scorn of early evening summer rain would be seized of turned out so fascinatingly, and it did procure a rather calming backdrop soundtrack to some extremely provocative take on the cholesterol wars. Nature absolutely did turn me on to the character of things, once again!
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