Hjerteklapp

My research

I received my doctorate from the University of Oslo in 2001 with the thesis Autonomic cardiovascular regulation in healthy subjects and patients with cardiovascular disease.

The work was carried out at the Department of Cardiology and the Clinical Research Laboratory, Ullevål University Hospital, and the Department of Internal Medicine, Bærum Hospital, in 1996–2001, supervised by Morten Rostrup. I learned to estimate heart rate variability and baroreflex sensitivity at the University Hospital of Groningen in the Netherlands, and a secondary aim of the thesis was to introduce these methods in our laboratory.

The main objective was to explore autonomic cardiovascular control, with emphasis on baroreflex sensitivity, heart rate variability and sympathetic responses to stress tests, in patients with cardiovascular disease and healthy people.

What we found

Chest pain and stress responses. Patients admitted to hospital with chest pain and later confirmed coronary artery disease had larger heart rate and blood pressure responses to a one-minute cold pressor test (hand in ice water) than chest pain patients without coronary disease: 12 vs 0 beats/min and 18 vs 2 mmHg.

Hypertension and sex. Autonomic cardiac regulation was generally blunted in people with high blood pressure compared to healthy subjects, with lower HRV and lower baroreflex sensitivity. Autonomic function was especially impaired in hypertensive women compared to hypertensive men. Sex, age, HDL cholesterol and blood pressure were independent explanatory variables of baroreflex sensitivity and HRV.

Two classes of blood pressure medication. In a European study of 145 patients in seven centres, we compared two calcium antagonists, verapamil and amlodipine, which lowered blood pressure equally. On verapamil, baroreflex sensitivity was higher, plasma noradrenaline lower and the sympathovagal balance shifted towards less sympathetic dominance. During a mental stress test (rapid mental arithmetic), noradrenaline and heart rate rose less on verapamil than on amlodipine.

Altitude. Healthy volunteers spent a week in a hypobaric chamber with stepwise ascent to a simulated 4,500 metres. Autonomic activity and reflexes were transiently blunted – HRV, baroreflex sensitivity, noradrenaline and the responses to stress tests all fell – contrary to the common view of hypoxia as a sympathetic activator. Even at a pressure equivalent to 2,400 metres, as in an airliner cabin, baroreflex sensitivity was reduced.

Later research

Meditation. With colleagues I later studied how the heart responds to Acem meditation, a nondirective technique. During 20 minutes of meditation, HRV increased in both the low- and high-frequency bands compared with rest, while respiration and heart rate were unchanged (Nesvold et al. Eur J Prev Cardiol 2012; 19: 773–80). Read more under HRV, breathing and meditation.

Chronic pain. In the Tromsø Study I took part in examining how chronic pain relates to changes in cardiovascular autonomic regulation, and what this means for comorbid high blood pressure in people with chronic pain (Bruehl et al. Pain 2018; 159: 119–27).

Chronic pain. In the Tromsø Study we compared 1,143 people with chronic pain with 5,640 pain-free controls. The pain group had lower HRV (SDNN, RMSSD and HF power) and lower baroreflex sensitivity, beyond the effects of age, sex and body mass index. Reduced cardiovascular regulation partly explained why people with chronic pain more often have high blood pressure. It was the largest study of the question to date (Bruehl et al. Pain 2018; 159: 119–27).

Lessons about method

Two methodological points from the thesis are still relevant when you look at HRV from watches and chest straps:

  • Present absolute values, not only ratios. The LF/HF ratio and normalised units can move in the same direction for opposite reasons (see How HRV is measured).
  • A higher heart rate is not necessarily more stress. Both in hypertension and at altitude, heart rate was higher while both sympathetic and parasympathetic markers were reduced. Heart rate may rise because autonomic control is generally weakened, bringing it closer to the heart’s intrinsic rate.

Papers in the thesis

  1. Sevre K, Rostrup M. Blood pressure and heart rate responses to cold pressor test in patients admitted to hospital due to chest pain. Blood Press 1999; 8: 110–3.
  2. Sevre K, Lefrandt JD, Nordby G, Os I, Mulder M, Gans ROB, Rostrup M, Smit AJ. Autonomic function in hypertensive and normotensive subjects: the importance of gender. Hypertension 2001; 37: 1351–6.
  3. Lefrandt JD, Heitmann J, Sevre K, et al. The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study. Am J Hypertens 2001; 14: 1083–9.
  4. Sevre K, Lefrandt JD, Eide I, Smit AJ, Rostrup M. Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects. Blood Press 2001; 10: 111–5.
  5. Sevre K, Bendz B, Nakstad AR, Hankø E, Hauge A, Kåsin JI, Lefrandt JD, Smit AJ, Eide I, Rostrup M. Reduced autonomic activity during stepwise exposure to high altitude. Acta Physiol Scand 2001; 173: 409–17.
  6. Sevre K, Bendz B, Rostrup M. Reduced baroreceptor reflex sensitivity and increased blood pressure variability at 2400 m simulated cabin altitude. Aviat Space Environ Med 2002 [VOLUME AND PAGES].

See also the review: Sevre K, Rostrup M. Undersøkelser av hjertefrekvensvariabilitet og baroreflekssensitivitet [Heart rate variability and baroreflex sensitivity]. Tidsskr Nor Lægeforen 2001; 121: 3059–64.