Hypertension Knowledge Centre
Understanding Hypertension
Hypertension and the Metabolic Syndrome
Hypertension is an important cause of mortality and morbidity. It is now widely recognised that elevated blood pressure is frequently associated with obesity, insulin resistance and dyslipidaemia. The clustering of these symptoms has given rise to the concept of the ‘metabolic syndrome’, which carries a high risk of diabetes and cardiovascular disease. One of the explanations for the association between raised blood pressure and co-morbidities of the metabolic syndrome is that they all reflect varying degrees of sympathetic overactivity.1
It has been demonstrated in several animal models of hypertension that sympathetic overactivity can initiate and maintain elevated blood pressure.2 In humans, a meta-analysis of a large number of studies showed that plasma norepinephrine levels in hypertensive patients were significantly higher than in normotensive controls (p<0.05).3 Sympathetic activation has been repeatedly documented in early phases of hypertension and may precede actual blood pressure elevation in some patients.4 The observation that sympathetic activity can be high in young subjects with borderline hypertension supports the idea that increased sympathetic activity is the cause rather than the consequence of blood pressure elevation.1
Overactivity of the sympathetic nervous system appears to be a pivotal factor in several coronary risk factors.2 For example, an increase in body mass index (BMI) is associated with an increased rate of sympathetic nerve discharge in skeletal muscle,5 and there is a correlation between BMI, body fat distribution and urinary norepinephrine excretion.6
An association of diabetes and hypertension has long been recognised. Elevated plasma insulin is a strong predictor of future diabetes, and sympathetic activation has been shown to be a major component of insulin resistance, both in clinical experiments7 and in humans with type 2 diabetes.8 Cardiac autonomic dysfunction (measured as abnormal heart rate variation to standardised tests) has been reported to occur in 30-50% of patients with diabetes, but also in 40% of obese patients without diabetes, indicating relative sympathetic overactivity both in diabetic and prediabetic states.9
Sympathetic overactivity is also implicated in renal disease,10 left ventricular hypertrophy,11 and congestive heart failure.12
Figure 1: Overactivity of the sympathetic nervous system may be a central feature linking hypertension with other components of the metabolic syndrome
Metabolic syndrome is a frequent condition. An epidemiological study of 4,483 subjects aged 35-70 years showed that 10-15% of people with normal fasting blood glucose had metabolic syndrome, and that the prevalence increased to 42-64% in those with impaired glucose tolerance/impaired fasting glucose. In people with type 2 diabetes the incidence of metabolic syndrome was 78-84%.13 The risk of coronary heart disease and stroke was increased three-fold in subjects with metabolic syndrome (p<0.001), and cardiovascular mortality was markedly increased (12.0% versus 2.2%, p<0.001). In this study, metabolic syndrome was defined as the presence of at least two of: obesity, hypertension, dyslipidaemia, microalbuminuria.
A framework has been suggested in which insulin resistance and metabolic syndrome contribute to cardiovascular complications through two main mechanisms: autonomic dysfunction (relative sympathetic overactivity) and endothelial dysfunction (figure 2).9 Both mechanisms are also capable of aggravating metabolic syndrome and insulin resistance.
(Figure 2: Framework showing how insulin resistance and metabolic syndrome may contribute to cardiovascular complications through relative sympathetic overactivity and endothelial dysfunction. Adapted from 9)
Given the important role of autonomic dysfunction in patients with metabolic syndrome, it would be rational that management of patients with hypertension should not be confined simply to lowering blood pressure, but should also take account of associated metabolic conditions.14
Sympathetic tone is regulated centrally by the cardiovascular control centres in the brainstem, of which one of the most important appears to be the rostral ventrolateral medulla (RVLM).15 This area contains several types of neuroreceptors, including α2-adrenoceptors and imidazoline I1-receptors, which exert a regulating influence on sympathetic activity.15