Abstract

Neurogenic factors are known to be important in the development of hypertension. Our current knowledge of the role of autonomic nervous system in chronic hypertension is, however, limited. The purpose of the present study was to evaluate the possible abnormalities in heart rate variability (HRV) and baroreflex sensitivity (BRS) in patients with long standing systemic hypertension compared to subjects without evidence of cardiovascular disease. A particular aim was also to examine whether genetic variation in the renin-angiotensin-aldosterone system (RAS) genes have an influence on cardiovascular autonomic regulation.

Case-control studies were carried out on a total of 280 normotensive and 214 hypertensive subjects drawn from a random middle-aged population originally recruited for an epidemiologic study of cardiovascular risk factors. The possible association of BRS with the genetic polymorphisms of renin-angiotensin-aldosterone system genes was studied in a cross-sectional study of 315 healthy controls. Genetic associations were also tested in a younger, independent population sample of 66 subjects. The effects of intensified antihypertensive treatment on autonomic cardiovascular control were evaluated in 33 hypertensive patients with poor blood pressure control.

Wide interindividual variation in both HRV and BRS was observed in normotensive as well as hypertensive subjects. Overall HRV and autonomic responses to a change in body posture were blunted in long-standing hypertension. Decreased HRV was mainly related to elevated blood pressure and obesity.

For the first time in a population-based study, it was confirmed that BRS is impaired in patients with long-standing hypertension despite adequate antihypertensive treatment. In contrast to HRV, BRS was reduced in hypertensive subjects also after adjustment for blood pressure and obesity. BRS also varied widely both between healthy and hypertensive individuals. The wide interindividual variation in the markers of autonomic cardiovascular regulation was not, however, completely explained by demographic variables, cardiovascular risk factors or lifestyle, suggesting a genetic component contributing to HRV and BRS.

The polymorphism in the aldosterone synthase (CYP11B2) gene was found to strongly associate with BRS in two independent random populations of apparently healthy subjects. The association was even stronger in the younger population. On the basis of the observations made in the older population, it seems possible that women are protected against the effect of age and blood pressure on BRS and tend to maintain the genomic influence longer.

Intensified antihypertensive combination therapy improved blood pressure control and caused regression of left ventricular hypertrophy, and resulted in significant improvements of HRV and BRS.

The present study shows that HRV and BRS are altered in long-standing systemic hypertension. Together with age, blood pressure and obesity, genetic factors seem to be important determinants of BRS. However, abnormal autonomic cardiovascular regulation does not seem to be an irreversible phenomenon, but can be partly restored by modern combination antihypertensive therapy.