Claims for these cardio drugs seem overstated; omega-3s enhance statin benefits 09/28/2016
The “saturated fat theory” of heart disease has crumbled fast over the past few years.
It's now clear that diets moderately high in saturated fat (and cholesterol) do not lead to cardiovascular disease, heart attacks, heart failure, stroke, or death.
Diets high in sugars and refined carbs pose a greater danger because they drive the inflammation that oxidizes cholesterol and leads to cardiovascular disease.
So the real danger is to combine lots of saturated fats and cholesterol with lots of sugars and refined carbs, as the average American does.
For more on this topic, see Big Sugar Paid Scientists to Pin Heart Disease on Saturated Fats.
In recent years, some doctors have called for very wide prescription of statins.
That's because clinical trials conducted in people with risk factors for cardiovascular disease — but without diagnosed cardiovascular disease — suggest that statins can significantly reduce the risk for heart-related deaths and deaths from all causes (Taylor F et al. 2011 and 2013).
The results of a recent clinical trial — called HOPE-3 — have prompted more doctors to call for wider prescription of statin drugs, even in people at low risk for cardiovascular disease.
But its results don't seem to support those calls.
Let's review the HOPE-3 trial, and take a closer look at statins, cholesterol, and the causes of cardiovascular disease.The HOPE-3 trial: Justification to prescribe more statins?
The five-year study was designed to test whether low-dose statins plus blood pressure drugs would two things (Yusuf S et al. 2016):
1) Reduce the risk of heart-related deaths
2) Produce better heart-health outcomes overall.
The 12,705 participants in the trial were relatively healthy, and classified as being at “intermediate” risk for suffering a heart attack or other adverse heart-related event.
About three-quarters of American men over the age of 55 and women over the age of 60 fit the definition of being at intermediate risk.
So the results of this trial — whether positive or negative — would apply to huge numbers of Americans, making it the subject of intense interest.
The researchers found that — compared with statins or blood pressure pills on their own — the so-called “polypill” combo produced better patient outcomes.
But it's important to dig into the details.
Reasons for skepticism
First, the subjects were already at relatively low risk of cardiovascular disease.
Second, only the participants in the upper third of risk for blood pressure problems experienced a significant reduction in cardiac events like heart attacks.
Finally, the results showed that the polypill combo produced “no effect” on the risk for heart-related deaths or non-fatal heart attacks and strokes.
In other words, results of the HOPE-3 don't present a strong argument for wider use of statins.
In fact, in an interview with cardiobrief.org, lead researcher Salim Yusuf, M.D., acknowledged that the trial results do not support widespread use of either the polypill or statins.
However, Dr. Yusuf offered a rather misleading characterization of its results: “Statins work beautifully, resulting in a high significant relative risk reduction of 25%.”
Relative risk: A misleading way to present study results
Unless a significant proportion of the people in a study group are likely to suffer an adverse heart-related event, or die from heart disease, a 25% reduction in relative risk is meaningless.
And when you take into account the small absolute risk for people in the HOPE-3 trial, that 25% reduction becomes trivial.
Out of the total, 3,180 participants were assigned to take the polypill, while 3,168 were assigned to take placebo pills.
Of the participants in the placebo group, 157 died from cardiovascular causes, suffered a non-fatal heart attack, or a non-fatal stroke.
By comparison, 113 participants in the polypill group experienced one of those adverse outcomes. That's a 28% reduction in risk. (In interviews, Dr. Yusuf often rounded that reduction down to 25%.)
Getting back to absolute risk, 3.5% of the polypill group (113) experienced one of these adverse effects, while 4.9% of the placebo group (157) experienced one of these adverse effects.
If you're someone in this intermediate risk group, who's never been diagnosed with heart disease, you might consider that minor reduction in risk worth the unknown adverse consequences of taking a statin drug for years or decades.
But that decision shouldn't be made in isolation.
Omega-3s may add benefits to statins
People taking statins may also benefit from omega-3 fish oil supplements.
A recently published Australian clinical trial found blood pressure and arterial benefits among people taking prescription statins who were given omega-3 fish oil (Chan DC et al. 2016).
The trial was conducted in people with high cholesterol caused by inherited genetics, or familial hypercholesterolemia (FH), which leads to elevated LDL cholesterol levels.
The researchers recruited 20 adults with FH who were already receiving statins, and randomly assigned them to receive either 4 grams per day of omega-3 fish oil or no supplements for eight weeks.
After a further eight-week ‘washout' period the participants were switched to the other group.
The results showed statistically significant improvements among the omega-3 group for large artery elasticity (9% increase), systolic and diastolic blood pressure (6% reductions for both measures), triglycerides levels (20% reduction), and apoB levels (8% decrease).
(Apo B or Apolipoprotein B is the form of LDL cholesterol most responsible for transporting cholesterol to tissues.)
While statin therapy may help reduce the risk of atherosclerosis (buildup of arterial plaque), it doesn't reduce other risks, including high blood pressure or triglyceride levels, and stiffening of the arteries.
As the authors wrote, “Given clinical evidence that arterial elasticity is an independent predictor of cardiovascular mortality and predictor of future coronary artery disease, our new data support the addition of [omega-3] supplementation to cholesterol-lowering therapy ...”.
The fact that they saw no link between the changes in large artery elasticity and blood pressure or other risk factors suggests that the improvement in these arteries was likely due to a direct effect of omega-3s on the artery wall.
According to the Australian team, “These findings are in agreement with other reports on the favorable effects of [omega-3] supplementation on cardio-metabolic risk factors.”
Diet and supplements can be highly effective
Changes in diet can lower cholesterol and triglyceride levels, improve cholesterol profiles, and reduce oxidized cholesterol levels.
And there are other ways to get the apparent benefits of statins, which include reduced inflammation.
A clinical trial published in 2009 showed that — in combination with omega-3 fish oil and advice to follow a Mediterranean-style diet — a red rice yeast supplement (a natural source of statins) worked as well as a leading prescription statin (Zocor) to lower LDL cholesterol.
Only 7 percent of the patients taking the yeast supplement developed muscle pain, versus about 20 percent of people taking statins, although that side effect often fades over time.
Further, diet alone can lower cholesterol and triglyceride levels, and other risk factors for cardiovascular disease.
And Mediterranean-style diets — ones that emphasize fruits and veggies, lean meats, and omega-3-rich fish, low-fat dairy, and nuts — can reduce the risk of cardiovascular disease and heart-related deaths.
Statin side effects
As Japanese researchers detailed in a disturbing summary, statins may actually promote some heart problems as they're alleviating others (Okuyama H et al. 2015).
Statins impair arteries and heart muscles by depleting CoQ10 — which is essential to muscle function — and blocking the synthesis of vitamin K2, which protects arteries from calcification.
(To deal with the CoQ10 problem, doctors often prescribe supplemental CoQ10 for patients taking statins.)
Alarmingly, a Japanese study in patients taking statins linked both low blood levels of omega-3s and low ratios of omega-3 to omega-6 fatty acids to the faster clogging of arteries.
For more on that, see Statins + Omega-Imbalance = Artery Clogs.
It's important to note that the statistically significant benefits seen in some clinical trials of statins may flow from their anti-inflammatory effects, rather than cholesterol-lowering effects.
Of course, exercise, a healthy omega-3/omega-6 balance in the body, and antioxidant-rich plant foods and medicinal herbs help dampen inflammation, with no adverse side effects.
Antiinflammatory herbs include rosemary, thyme, oregano, cumin, holy basil, ginger, turmeric, and extracts of these and many others.
Cholesterol: An oversimplified story
Decades of oversimplification by doctors and the media have led us astray.
Cholesterol has a wide range of health effects, depending on the fat/protein package in which it's carried through the bloodstream.
The best known cholesterol carriers are LDL (low-density lipoprotein) and HDL (high-density lipoprotein), but there are many others.
Despite what we often hear, high total cholesterol levels are not strongly linked to significantly greater risk of cardiovascular disease or heart-related deaths.
And you can't predict someone's risk based on their blood levels of total cholesterol, so-called “good” HDL cholesterol, or “bad” LDL cholesterol.
We now know that blood levels of triglycerides, inflammation, and of lesser-known form of cholesterol – such as VLDL – reveal more about someone's risk.
That's true for two reasons, which have become apparent relatively recently:
• People's genetic profiles can strongly influence the effects of diet and lifestyle on cardiovascular risk.
• Each of several types of “bad” LDL and “good” HDL cholesterol exert very different effects, making a mockery of those wildly oversimplified labels.
But those critical distinctions rarely get made in the popular press, or in enough doctors' offices.
The true villains: Excess sugar, carbs, omega-6 fats, and inflammation
Cholesterol is essential to brain, nerve, and overall health, and is made in the liver.
Chronic inflammation in the body leads to oxidation of cholesterol.
And oxidized cholesterol is recognized as a key cause of damage to artery walls.
This artery damage prompts an immune response that includes inflammation and production of immune-system cells.
Ironically, the body's immune response to artery damage worsens matters, leading to a buildup of unstable arterial plaque that can burst, releasing artery-constricting clots.
The chief drivers of chronic inflammation include sedentary lifestyles, stress, and diets — such as the standard American diet — high in sugars, refined carbs, certain saturated fats, and/or omega-6 vegetable oils.
- Lonn EM, Bosch J, López-Jaramillo P, Zhu J, Liu L, Pais P, Diaz R, Xavier D, Sliwa K, Dans A, Avezum A, Piegas LS, Keltai K, Keltai M, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Parkhomenko A, Khunti K, Toff WD, Reid CM, Varigos J, Leiter LA, Molina DI, McKelvie R, Pogue J, Wilkinson J, Jung H, Dagenais G, Yusuf S; HOPE-3 Investigators. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2009-20. doi: 10.1056/NEJMoa1600175. Epub 2016 Apr 2.
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- Yusuf S, Lonn E, Pais P, Bosch J, López-Jaramillo P, Zhu J, Xavier D, Avezum A, Leiter LA, Piegas LS, Parkhomenko A, Keltai M, Keltai K, Sliwa K, Chazova I, Peters RJ, Held C, Yusoff K, Lewis BS, Jansky P, Khunti K, Toff WD, Reid CM, Varigos J, Accini JL, McKelvie R, Pogue J, Jung H, Liu L, Diaz R, Dans A, Dagenais G; HOPE-3 Investigators. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2.