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Circulation. 2005;112:e368-e369
doi: 10.1161/CIRCULATIONAHA.105.569038
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(Circulation. 2005;112:e368-e369.)
© 2005 American Heart Association, Inc.


Correspondence

Letter Regarding Article by Hemingway et al, "Does Autonomic Function Link Social Position to Coronary Risk?: The Whitehall II Study"

Berthold Bein, MD; Robert Hanss, MD; Jens Scholz, MD; Peter H. Tonner, MD

Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

To the Editor:

We read with interest the article by Dr Hemingway and colleagues1 reporting the results from the Whitehall II study, with special emphasis on heart rate variability (HRV) and social position. That article addresses the impact of the social position of a large group of male civil servants in the United Kingdom on HRV. We agree with the authors that HRV is a useful tool to determine the balance of the autonomic nervous system and thus may be able to serve as a predictor of individual cardiovascular risk; however, there are some points we wish to comment on.

First, the authors measured HRV once for a 5-minute interval. Unfortunately, they do not report on the time of day the measurement was performed and whether this time was comparable between study participants. It is well known that HRV is strongly influenced by the circadian rhythm.2 Therefore, a 24-hour recording interval would have been more appropriate. More important, concurrent medication may have a paramount effect on HRV measurements, which is particularly relevant if patients are taking cardiovascular drugs such as ß-blockers.3 Was the study balanced in this respect? Second, the results are without doubt statistically significant (mainly because of the large sample size). Whether or not a difference between 68 bpm (high employment grade) and 71 bpm (low employment grade) is of clinical relevance, however, appears questionable at best. The same applies to the various HRV data obtained. Interestingly, the authors did not analyze the low-frequency/high-frequency ratio, which was recently shown to be a sensitive and specific tool for determination of sympathetic activation.4 When we calculated the low-frequency/high-frequency ratio for the various subgroups defined by the authors, the differences were less than impressive.

In conclusion, although HRV may clearly be different between groups, an overinterpretation of a single 5-minute HRV measurement as a link of social status to cardiovascular disease is not warranted.


*    Acknowledgments
 
None.


*    References
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*References
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  1. Hemingway H, Shipley M, Brunner E, Britton A, Malik M, Marmot M. Does autonomic function link social position to coronary risk? The Whitehall II Study. Circulation. 2005; 111: 3071–3077.[Abstract/Free Full Text]
  2. Huikuri HV, Niemela MJ, Ojala S, Rantala A, Ikaheimo MJ, Airaksinen KE. Circadian rhythms of frequency domain measures of heart rate variability in healthy subjects and patients with coronary artery disease: effects of arousal and upright posture. Circulation. 1994; 90: 121–126.[Abstract/Free Full Text]
  3. Tuininga YS, Crijns HJ, Brouwer J, van den Berg MP, Man in’t Veld AJ, Mulder G, Lie KI. Evaluation of importance of central effects of atenolol and metoprolol measured by heart rate variability during mental performance tasks, physical exercise, and daily life in stable postinfarct patients. Circulation. 1995; 92: 3415–3423.[Abstract/Free Full Text]
  4. Hanss R, Bein B, Ledowski T, Lehmkuhl M, Ohnesorge H, Scherkl W, Steinfath M, Scholz J, Tonner PH. Heart rate variability predicts severe hypotension after spinal anesthesia for elective cesarean delivery. Anesthesiology. 2005; 102: 1086–1093.[Medline] [Order article via Infotrieve]

 

Response

Harry Hemingway, FRCP; Martin Shipley, MSc; Eric Brunner, PhD; Annie Britton, PhD; Michael Marmot, FRCP

International Centre for Health and Society, Department of Epidemiology and Public Health, University College London Medical School, London, UK

Marek Malik

Cardiological Sciences, The Medical School St George’s Hospital, London, UK

The letter by Bein and colleagues raises important points that, based on the further analyses presented here, allow us to demonstrate the robustness of our conclusions.1 First, although participants from lower civil service employment grades were slightly more likely to have their HRV measurements before 11 AM (33%) than were those with medium (26%) and high (26%) grades of employment, adjustment for time of day had no or trivial effects on the employment grade differences in heart rate and heart rate variability.

Second, we also adjusted the employment grade effects for use of ß-blockers or a more inclusive group of all cardiovascular medications. These adjustments strengthened the effect on heart rate and weakly attenuated the effects on heart rate variability, with all remaining significant at P≤0.05.

Third, we agree with Bein et al that 24-hour recordings would be informative. Indeed, in the discussion, we stated that they may offer a "better characterization of these relationships."

Fourth, we do not accept that our findings reach only statistical significance. The differences in components of the metabolic syndrome are large and of biological significance; for example, the difference in systolic blood pressure between top and bottom quartiles of heart rate variability measures exceeds half a standard deviation.

Fifth, it was not our research objective to determine effects that might have an impact on clinical decision making in individual patients. We sought to test an etiological association in a general population. It is well recognized that a mean difference between 2 populations that is modest in clinical terms can have important consequences in public health terms.2 For example, lowering the mean blood pressure of a population by 5 mm Hg has been estimated to reduce risk of coronary events by 21%.3

Sixth, there is an employment grade gradient in the low frequency/high frequency ratio of 2.77 (high grade), 2.89 (medium), and 3.01 (low grade; P for trend 0.08). This trend is consistent with our findings for the other measures. Indeed, because interpretation of the ratio remains complex (with parasympathetic activity influencing numerator and denominator) and previous findings are conflicting,4 we, like many groups, elected not to report it.

We thank Bein et al for their comments and remain of the conclusion that chronically impaired autonomic function may link social position to different components of coronary risk in the general population.


*    Acknowledgments 
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up arrowReferences
*Acknowledgments 
down arrowReferences 
 
Disclosures

M. Malik receives lecture fees from GE Medical Systems. The other authors report no conflicts.


*    References 
up arrowTop
up arrowReferences
up arrowAcknowledgments 
*References 
 

  1. Hemingway H, Shipley M, Brunner E, Britton A, Malik M, Marmot M. Does autonomic function link social position to coronary risk? The Whitehall II Study. Circulation. 2005; 111: 3071–3077.[Abstract/Free Full Text]
  2. Rose G. The Strategy of Preventive Medicine. Oxford, UK: Oxford University Press; 1992.
  3. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J. Blood pressure, stroke, and coronary heart disease, part 1: prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335: 765–774.[CrossRef][Medline] [Order article via Infotrieve]
  4. Britton A, Hemingway H. Heart rate variability in healthy populations: correlates and consequences. In: Dynamic Electrocardiogr. Malik M, Camm AJ, eds. New York, NY: Blackwell Futura; 2004.




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