Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function, 2010, Hurwitz, Klimas et al

https://portlandpress.com/clinsci/article-abstract/118/2/125/68670
Scihub
2010 paper

Barry Hurwitz; Virginia Coryell; Meela Parker; Pedro Martin; Arthur LaPerriere; Nancy Klimas; George Sfakianakis; Martin Bilsker

Abstract
The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume).

The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body mass.

Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups.

Of the CFS subjects with a TBV deficit (i.e. ≥8% below ideal levels), the mean±S.D. percentage deficit in TBV, PV and RBCV were −15.4±4.0, −13.2±5.0 and −19.1±6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels. Analyses indicated that the TBV deficit explained 91–94% of the group differences in cardiac volume indices. Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index.

Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition. Further study is needed to address the extent to which the cardiac and blood volume alterations in CFS have physiological and clinical significance.

 

Participants

The CFS participants (56 of them) came from a prior study (MIAEPO). CFS diagnosis was based on the participant providing evidence of a diagnosis by a physician, later confirmed by an interview and questionnaires. 24 of the control participants came from this study - low blood volume was a basis for excluding control participants, so these ones all had normal blood volume. The aim of the previous study was to identify CFS participants with low red blood cell volume, so there is some potential for bias in selection.

Two sets of control participants were selected from a previous study (MARCH) - one set 37 healthy sedentary and 32 healthy non-sedentary. These participants were selected in order to match the CFS participants in terms of gender, age, race and BMI. These control participants weren't previously evaluated for low blood volume.

So, that is the 146 participants: 56 CFS participants from MIAEPO and 90 controls (24+37+32 - yes, that doesn't quite add up). Edit - 3 of the controls had data excluded for 'technical reasons'. Of the 90 controls, 58 were sedentary and 32 were non-sedentary. There's an explanation of how 'sedentary' was evaluated - an assessment of energy expended on physical activity was made.

The 56 CFS participants, were divided into two groups - severe (30) and not severe (26). This classification was odd, certainly not in keeping with how we normally talk about 'severe'. It appears that PEM wasn't evaluated and even 'post-exertional fatigue' was not mandatory. And, someone could have had symptoms at a moderate or severe level in the past but not have them now, and still be rated as 'severe'.

So, there's the CFS participants ('severe' and 'not severe') and the controls (sedentary and not sedentary).

 

Blood volume studies

So, this comparison only involved the participants from the MAIEPO study (56 CFS and 21 controls), using data from that study. Note the 21 controls versus the 24 that started - the data for three was excluded for 'technical reasons'.

The total blood volume and plasma blood volume was measured with two techniques:
1. Dual tag blood volume assessment, uses radioactive isotopes. It's claimed to be the gold standard technique.
2. For 18 participants, due to the unavailability of an isotope, the plasma volume was assessed using a different technique. The study reported that the alternative technique had been validated and found to give a result within 3.3% of the dual tag approach. However, we don't know which participants (CFS severe or not severe, or controls) were measured with this other technique.

Total blood volume was calculated by adding the plasma volume and the RBCV figures. Differences from ideal values were calculated taking into account age, gender, weight and height.

Table 4 gives the results, part of which is shown below:


It looks as though the sedentary controls might not be very typical, as might be expected given the screening for the study (which excluded any controls with blood volume values below a normal range). The sedentary controls had an average of 12% more plasma volume than ideal for people of the same age, gender, weight and height.

The differences in blood volume from this small study do look interesting, with people with ME/CFS possibly having lower blood volumes than sedentary controls. But the issues with a control group specially selected to exclude low blood volumes, the different measurement techniques and the correction process for body weight result in some question marks around this finding.