Statins, Heart Disease and Inflammation

There are a few lines of evidence. One is that people with immune diseases like rheumatoid arthritis and lupus have a raised risk of heart attacks. It’s also known that white blood cells and immunological hormones assist cholesterol damage in arteries.

And it is also known that statins - cholesterol-lowering medications - reduce the risk of heart attacks more than you’d expect from their cholesterol reduction, and they have immune effects.

Summarizing the findings from the three recent papers, they suggest that while cholesterol lowering is still vital, reducing inflammation - the immune reaction in arteries - is important too.

In one study of people on statins, the lower the inflammation, the lower the heart attack risk. In another study of people on a statin, the lower the bad form of cholesterol and inflammation, the slower artery blockage progressed. And a third study of markers of inflammation showed an association with the risk of heart disease.

Some lifestyle changes may help lower inflammation, like exercise and diet if you don’t like fancy medications, but that’s yet to be proven conclusively.

Dr. Norman Swan

For Reference

Title: New England Journal of MedicineAuthor: Nissen S et al, Statin therapy, LDL cholesterol, C-reactive protein and coronary heart disease. URL: http://content.nejm.org/ 2005, vol 352, pp 29-38.
Title: New England Journal of MedicineAuthor: Ridker PM et al, C-reactive protein levels and outcomes after statin therapy. URL: http://content.nejm.org/ 2005, vol 352, pp 20-28..
Title: New England Journal of MedicineAuthor: Ehrenstein MR et al, Statins for atherosclerosis - a good as it gets? URL: http://content.nejm.org/ 2005, vol 352, pp 73-75.
Title: New England Journal of MedicineAuthor: Pai J et al, Inflammatory markers and the risk of coronary heart disease in men and women. URL: http://content.nejm.org/ 2004, vol 351, 2599-2610.
ABC Flameez

The Connection Between Heart Disease And Inflammation

In 1997, a study showed, for the first time, the link between C-Reactive Protein (CRP) and heart disease. The public began to hear rumblings about testing for CRP a few years later. Some public health advisors began to say that CRP levels were as important, if not more important, than cholesterol levels in predicting heart disease. Was it just one study or have the results been repeated? Several studies have supported CRP as an indicator of risk of heart attack, and more have elaborated on the relationship between infection, CRP, and heart disease.

C-Reactive Protein is produced by the body when inflammation is present. Inflammation is part of the body’s immune reaction to infection and injury. Why would inflammation be related to heart disease and heart attack? While the specific cause and effect is so far unknown, there is clearly a strong correlation between inflammation and heart attack.

In fact, not only is the relationship between inflammation and acute heart attack clear, but studies also definitively indicate that inflammation is also related to non-acute heart disease as well as high blood pressure. (Women’s Heath Study 1998)

First in 1997, the Physician’s Health Study (a large, ongoing survey of initially healthy men) reported that C-reactive protein was a indicator of heart attack risk. Subsequently in 1998, the Women’s Health Study (a large, ongoing survey healthy, post-menopausal women) revealed a similar finding, but added a link between CRP and stroke (Sesso 2003 BYU) and general cardiovascular disease.

The American Heart Association list the following risk factors for developing heart disease or suffering a heart attack: Increasing age, male gender, heredity (including race,) smoking, high cholesterol, high blood pressure, inactivity, obesity and overweight, diabetes, excess alcohol consumption, and stress.

Most of these heart disease risk factors are directly related to levels of inflammation. Heart attack risk factors directly related to high levels of inflammation include smoking, high blood pressure, inactivity, obesity, diabetes, excess alcohol consumption, and sometimes stress (M. Collins 2001.)

The good news is that even if there’s nothing we can do to keep ourselves from getting older or being male, there’s still a lot of room for prevention by tackling the causes of inflammation.

Keeping ourselves healthy and free of infection is one avenue. A recent study showed a distinctly higher level of UTI (urinary tract infection) in patients admitted for acute coronary syndrome (J.B.Sims 2004); an earlier study concluded that people with periodontal infections carried higher levels of CRP. (Noack 2001) As we know of the link between CRP, infections, and heart disease, it is logical to conclude that simply reducing our infections will help prevent heart disease.

The Connection

Anti-Inflammatory Action Plan

Once thought to be a simple problem of too much cholesterol, it is now widely accepted that inflammation also plays a central role in the atherosclerotic process. Inflammation, measured by a factor in blood called C-reactive protein (CRP), can lead to heart attack or stroke. Inflammation may also raise the risk of hypertension, obesity and eye disease.

Inflammation, High Blood Pressure & AMD

Picture your blood vessels as a system of pliable pipes. When more blood needs to flow through them in a hurry, they have the flexibility to expand. When less flow is required, they can contract-except, apparently, when they’re subject to inflammation. New research suggests that with inflammation, vessels become stiff and less flexible. So when a high volume of blood has to push through the constricted arteries, it creates more pressure against the artery walls and results in high blood pressure. Over time, hypertension weakens vessel walls and paves the way for heart attacks and stroke.

The inflammation-high blood pressure connection recently emerged in a Harvard University study. CRP was measured in 20,000 women who were followed for an average of 8 years. Those with the highest level of CRP at the start were about 50% more likely to end up with hypertension compared to those who started out with the lowest levels. Even women who began with relatively low blood pressure were more apt to develop hypertension if their CRP was on the high side. A CRP over 3.5 mg/L was considered quite high and was most strongly linked with developing hypertension. But even CRP in the range of 1.7-3.5 was associated with greater hypertension risk (1). CRP levels appear to raise the risk for age-related macular degeneration (AMD) as well. In the AREDS trial, those with advanced AMD had significantly higher CRP than those without this condition. Higher CRP levels were also observed in those with intermediate stage AMD (2).

Steps to Lower Inflammation

Shed extra weight. A recent study suggests that one of the most important ways to keep CRP levels down is to lose extra weight. A Tufts University study compared the weight-loss effectiveness of four different diets: Weight Watchers, Atkins, Zone and Ornish. All four diets reduced CRP, though the low-fat Ornish diet lowered it the most and promoted the greatest weight loss (3). According to the Tufts investigators, one of the best predictors of CRP is abdominal fat, and losing weight around the middle works well for lowering CRP.

Go with a lower fat, produce-rich diet. What you eat might be as important as eating to lose weight. A large scale study compared two diet patterns: one was the typical Western style diet, with more red meat, processed meat, french fries, high-fat dairy, refined grains and sweets. The other diet was high in fruits and vegetables, poultry, fish, whole grains and beans. There was only a modest difference between the two diets in terms of total, LDL and HDL cholesterol. But compared to the healthier diet, men eating the crummy diet had higher levels of CRP (4).

Fold in more fish. The omega-3 fatty acids in fish (EPA, DHA) can create more of the prostaglandins that suppress inflammation, while other fats (mostly omega-6) create prostaglandins that encourage it. A number of studies have shown that fish oil supplements or diets high in fish, can reduce the symptoms of inflammatory rheumatoid arthritis. Many scientists think that eating a better balance of omega-3 to omega-6 fatty acids could also potentially cut the risk of heart disease.

Take a “multi” supplement. Research suggests that inflammation may deplete antioxidant stores. Lower blood levels of lutein, lycopene, carotenes, vitamin C and selenium were significantly related to higher CRP levels in a recent study. This association held even after adjusting for many other factors that can affect CRP such as smoking, aspirin use, age, exercise, etc. Preliminary findings also indicate that vitamin E may be useful in lowering CRP (6).

Action Plan

References

1. Sesso HD et al. C-reactive protein and the risk of developing hypertension. JAMA 290:3000-2, 2003.

2. Seddon JM et al. Association between C-reactive protein and age-related macular degeneration. JAMA 291:704-10, 2004.

3. Schaefer EJ et al. Tufts University Health and Nutrition Letter. February, 2004.

4. Kerver JM. Dietary patterns associated with risk factors for CVD in healthy US adults. AJCN 78:1103-10, 2003.

5. Ford ES et al. C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among US adults. Eur J Clin Nutr. 57:1157-63, 2003.

6. Devaraj S and Jialal L. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med 29:790-2, 2000.

The Statin Scam

The television ad featuring artificial heart inventor Dr. Robert Jarvik, who by the way can’t row a skull, and never practiced medicine, claims that Lipitor will lower heart attack risk by 36%. Now, who wouldn’t want to do that?

However, the fine print required says, “in a large clinical study 3% of people taking placebo had a heart attack and 2% of those taking Lipitor had a heart attack.” Let’s do the math.

For every 100 people in the trial that lasted for 3 1/2 years, three people on placebo, and two people on Lipitor had heart attacks-that is one less heart attack for every 100 people. In other words, 100 people had to take the drug for 3 1/2 years to prevent one heart attack. What this really means is 99 out of 100 people taking the drug had no benefit.

This is explained in a little known statistic called Number Needed to Treat (NNT). In the case of Lipitor, 100 patients would have to be treated for 3 1/2 years to possibly eliminate one heart attack. Let’s compare that to today’s antibiotic treatment to eradicate ulcer causing H. pylori stomach bacteria.

The NNT is 1.1, which means, give the antibody to 11 people and 10 will be cured. Several recent scientific papers peg the NNT for statins at 250. Dr. Jerome R. Hoffman, Professor of Clinical Medicine at UCLA asks:

“What if you put 250 people in a room and told them that they each would have to pay over $1000 per year for a medicine they must take every day, that may give them diarrhea and muscle pain, and that 249 would get no benefit, how many would take that?”

Marketing over Medicine!

Drug companies have a responsibility to their shareholders to make a profit, and we need them to develop new medicines. However, when they grossly overstate the benefits and spend huge amounts of money influencing physicians it turns bad and leads to potential corruption.

The National Cholesterol Education Program, (NCEP) 2004 guidelines that lowered the targets for cholesterol treatment and recommended many more Americans take statins was issued by a panel on which 8 of 9 experts at financial ties to the drug industry.

“The guideline and process went awry” says Dr. Henry C. Barry of the Michigan State University College of Medicine. Dr. Barry and 34 other experts sent a petition of protest to the National Institutes of Health, saying the evidence was weak and the panel biased because of its ties to the drug industry.

I and all other physicians whose speak out take great risks-medicine and government agencies do not like criticism. At a recent meeting, a prominent statin boosting physician who advises the NCEP says that Dr. Rodney A. Hayward, Professor of Internal Medicine at the University of Michigan Medical School “should be held accountable in a court of law for doing things to kill people” because Dr. Hayward had the audacity to suggest that “current evidence supports ignoring LDL cholesterol altogether.”

We would expect this kind of vitriol from zealots and extremists not from government agencies or scientists. If we spent a fraction of the money that we do on cholesterol testing, cholesterol lowering drugs, and doctor visits on educating people about proper diet, exercise and weight loss we would be far healthier.

–Dr. Dwight Lundell