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Are Stiffened Arteries Increasing Cardiovascular Risk in ME/CFS and Fibromyalgia?

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Reprinted with the kind permission of Cort John and Health Rising

Systrom, Scheibenbogen and others have has found evidence of microcirculatory problems in chronic fatigue syndrome (ME/CFS) and fibromyalgia, but what about the big blood vessels – the arteries?

These muscular, but flexible, tubes transport oxygenated blood under high pressure from the heart to the organs and muscles. They need to be strong enough to withstand the highest circulatory pressures in the body and supple enough to quickly respond to changes in blood pressure and wind their way through the body.

Given the crucial role they play, it’s perhaps no surprise to find out that they are complex indeed. Composed of three layers of smooth muscle, connective tissue and collagen, they pulse or enlarge when the heart beats and relax when the heart rests.

The Study

Effects of Post-Exertional Malaise on Markers of Arterial Stiffness in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This New Zealand study chose to study something called “arterial stiffness”, which describes how elastic the arteries are and how well they comply or react to the changes in blood pressure they’re constantly experiencing. Increased levels of arterial stiffness have been shown to be a “strong predictor” of an increased risk of stroke, heart failure, atherosclerosis, heart attack, and coronary artery disease.

They used a measure called AIx to assess arterial stiffness. Higher AIx levels indicate increased arterial stiffness. The New Zealand study was very clever. Recognizing that exercise might induce a state of oxidative stress/inflammation that resulted in arterial stiffness, they put people with ME/CFS and healthy controls on a bike, had them pedal to exhaustion, and measured their AIx before and then 48 and 72 hours later. (Dr. Klimas has reported that extensive monitoring before, during, and after exercise indicates that exercise triggers a burst of inflammation and oxidative stress in ME/CFS.)

Thirteen years ago, Spence found evidence of arterial stiffness in ME/CFS, but no one until now has assessed it after exercise. Seventeen people with ME/CFS and 16 healthy controls engaged in a maximal exercise test. Some returned 48 hours later, and some 72 hours later, to assess their levels of arterial stiffness.

Results

As so often happens, the results were similar at baseline in the ME/CFS and healthy controls but adding an exercise stressor changed things. Two days after exercise, the healthy controls’ AIx (or arterial stiffness) had actually declined, i.e., indicating that the intense exercise had had a healthy effect on the healthy controls’ arteries. This is believed to occur when exercise-induced nitric oxide, prostaglandin and endothelin levels relax the arteries, allowing them to dilate more and leaving them suppler and more responsive.

No change, however, was found in AIx in the people with ME/CFS after 48 hours, i.e., while their arterial stiffness didn’t increase, their arteries also didn’t receive any of the benefits from exercise that the healthy controls did. A big spike in oxidative stress and inflammation – and ultimately, arterial stiffness – brought on by a broken energy production system being pushed past its limits in ME/CFS seems to make total sense.

It’s not a definitive study – it was too small for that – but it’s another in a long stream of studies that find exercise – long thought to be a kind of universal healer – actually makes things worse in ME/CFS. While the study needs to replicated, finding a significant difference in arterial stiffness between people with ME/CFS and healthy controls two days after exercise was remarkable.

What’s clearly needed next are more comprehensive studies that measure arterial stiffness in the hours and days after an exercise stressor. Nobody would probably be shocked to see arterial stiffness dramatically increase shortly after exercise in ME/CFS and then slowly wind back down to baseline levels. Assessing measures of oxidative stress and inflammation at the same time should, of course, be done as well.

This study comes about a year after Scheibenbogen’s team found evidence of endothelial dysfunction in about half of the ME/CFS patients. These endothelially challenged ME/CFS patients were functionally more limited and had more severe fatigue-related and immune-related symptoms (sore throat, painful lymph nodes). Scheibenbogen also believes that adrenergic antibodies may be interfering with blood vessel functioning, and she and Wirth have proposed that sympathetic nervous system activation is narrowing the arteries.

We also recently saw evidence of low blood flows to the brain upon standing – perhaps brought on by low CO2 levels – that are narrowing the arteries.

It seems the deeper researchers dive into the exercise issue, the more they find.

Increased Cardiovascular Risk?

This study also brings up the issue of what cardiovascular risks diseases like ME/CFS and fibromyalgia may pose.

Several studies – including one large one – have found increased arterial stiffness in FM. One linked the arterial stiffness to more severe symptoms, and proposed that activation of the fight/flight or sympathetic nervous system played a role.

Two studies have also found a moderately increased risk (50%) of coronary heart disease in fibromyalgia. As a group, people with FM had more diabetes, hypertension, hyperlipidemia, congestive heart failure, cerebral vascular diseases, depression, and anxiety than the reference cohort they were compared to.

While those comorbid conditions were more common in FM, the good news was that people with FM who did not have those cardiovascular conditions (diabetes, hypertension, hyperlipidemia, congestive heart failure, cerebral vascular diseases) actually had a somewhat lower risk of heart disease than the reference population.

The authors suggested that chronic stress, including, in some patients, early lifetime stressors, increased sympathetic nervous system activity and reduced parasympathetic nervous system activity. They noted the reduced heart variability results found in FM, which are a known risk factor for heart disease.

Oxidative stress and inflammation can wreak havoc on our arteries. Inflammation can damage the endothelial lining on the inside of the arteries, allowing cholesterol and white blood cells into the inner arterial layers, hardening and narrowing the diameter of our arteries (atherosclerosis). People who smoke, have high blood pressure, insulin resistance, are overweight, who don’t exercise, or have unhealthy diets are all at risk of atherosclerosis.

Increased levels of oxidative stress can impact the blood vessels and have been found in both fibromyalgia and ME/CFS. Plus high levels of oxidative stress factors and/or decreased levels of the protective antioxidants have twice been associated with increased symptoms in ME/CFS and FM.

Several studies have found “unfavorable lipid profiles” that could increase the risk of atherosclerosis in ME/CFS. Fibromyalgia studies have had mixed results with several finding unfavorable lipid profiles and others not. Low levels of the healthy cholesterol (HDL-C) have been found in ME/CFS. A 2005 study found increased levels of oxidized lipids and decreased HDL-C in ME/CFS patients with risk factors (high blood pressure and/or obesity).

Spence’s 2008 ME/CFS study found increased arterial stiffness and significantly increased markers of inflammation and oxidative stress (C-reactive protein, 8-iso-prostaglandin F, isoprostanes, oxidized LDL) which could be damaging the arterial walls. Spence concluded that “inflammation and oxidative stress may result in an increased risk of future cardiovascular events” in ME/CFS.

In 2009, Maes concluded that chronic low grade inflammation, increased oxidative and nitrosative stress, reduced levels of antioxidants, and healthy fatty acids could predispose people with ME/CFS to cardiovascular issues.

A small 2012 study of women with ME/CFS found high levels of “bad” fats, low levels of the “good” fats and signs of oxidative stress (increased malondialdehyde levels).

Large epidemiological studies are clearly needed to assess cardiovascular risk in FM and ME/CFS. People with ME/CFS can help further our understanding in this (and other) areas by participating in the Solve ME/CFS Initiative’s You+ME Patient Registry. 

Conclusion

At least four studies have found increased arterial stiffness in fibromyalgia, and this is the second study to find altered arterial stiffness – a risk factor for cardiovascular disease – in ME/CFS. While baseline levels of arterial stiffness were normal, people with ME/CFS had elevated levels of arterial stiffness relative to a healthy control group 48 hours after exercise. Exercise decreased arterial stiffness – leaving the arteries more supple and responsive to blood pressure changes – in the healthy controls but not in the people with ME/CFS. The inability of exercise to improve arterial stiffness could contribute to post-exertional malaise.

Larger, more comprehensive studies are needed to validate the findings and to determine what happens to arterial stiffness in the hours and day following exercise in ME/CFS.

Increased arterial stiffness is a risk factor for cardiovascular diseases. Note that increased arterial stiffness was not found at baseline in this study – but was in an earlier study – and has been found several times in FM. Studies indicate that people with ME/CFS/FM also display a number of risk factors for cardiovascular illnesses such as increased oxidative stress, unfavorable lipid profiles, reduced heart rate variability, as well as low exercise levels and increased levels of stress. On the plus side, high blood pressure is rarely mentioned in connection with these diseases (but can be found in hyperadrenergic POTS – which is found in ME/CFS).

Several Taiwanese studies suggest people with FM may have a moderately increased risk of coronary heart disease and/or stroke. (Note, though, that an FM patient’s chance of having either is still quite low.)

Given the risk factors present, large epidemiological studies are needed in both ME/CFS and FM to assess cardiovascular risk. People with ME/CFS can, however, help further our understanding in this area by participating in the Solve ME/CFS Initiative’s You+ME Patient Registry.

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